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Objective: To obtain the simplest definition of minimal disease activity (MDA) and to compare it with published proposed definitions of MDA in patients with RA., Methods: Two hundred and fourteen patients with long-standing RA (LSRA) were evaluated for clinical and laboratory parameters. Factor analysis was performed to remove redundant variables included in the core set measure for MDA definition stated by the OMERACT. Receiver operating characteristic (ROC) curves analysis allowed to obtain optimal cut-off predictors of a 28-joint disease activity score (DAS28) < or =2.85. These were tested in 112 LSRA and 95 early-onset RA (ERA) patients., Results: Factor and ROC curve analysis showed that the best predictors of a DAS28 < or = 2.85 in LSRA cohort were: (i) ESR <20 mm/h (sensitivity: 80%, specificity: 54%); (ii) swollen joint count (out of 28) < or =2 (sensitivity: 95%, specificity: 74%); (iii) patient global assessment (0-100) < or =15 (sensitivity: 78%, specificity: 78%); and (iv) HAQ (0-3) < or =0.5 (sensitivity: 91%, specificity: 61%). To each of these four criteria we assigned a value of 1 when it was satisfied (score ranging: 0-4). The cut-off with the highest overall accuracy for identifying RA patients with DAS28 < or = 2.85 was a score > or =3. We adopted these four parameters in order to define the residual MDA (RMDA). Comparing RMDA criteria, in distinct 112 LSRA and 95 ERA patients, with OMERACT, Simplified Disease Activity Index and Clinical Disease Activity Index definitions of MDA, we found a good agreement in the LSRA cohort and moderate agreement in the ERA cohort., Conclusions: HAQ, PaGA, SJC28 and ESR allow identification of RA patients with an RMDA. The RMDA criteria behaves similarly to OMERACT definitions, but appears more simple and feasible.

The metastasizing capacity of the rat pancreatic adenocarcinoma BSp73ASML (ASML(wt)) is strikingly reduced by a knockdown of CD44v4-v7 (ASML(kd)). We used this model to analyze the role of the CD44 variant isoform (CD44v) in (pre)metastatic niche formation. Intrafootpad injections of ASML(wt)-, but not ASML(kd)-conditioned medium (CM), strongly promote settlement of ASML(kd) cells in lymph nodes and lung. Fractionation of CM revealed a contribution by a soluble matrix and exosomes, where the CD44v6-containing ASML(wt)-soluble fraction can complement ASML(kd)-exosomes, but not vice versa. This implies that exosomes are the final actors, are CD44v-independent, but require a soluble matrix, which depends on CD44v. Analyzing the composition revealed that only the ASML(wt)-matrix contains c-Met and urokinase-type plasminogen activator receptor. In vitro, mostly ASML(wt)-exosomes promote proliferation and induce gene expression in metastatic organ cells. However, in vivo corresponding changes in the (pre) metastatic organ are only observed when both, exosomes plus the soluble matrix, are provided. Thus, neither CD44v nor exosomes alone suffice for (pre)metastatic niche formation. Instead, CD44v suffices for assembling a soluble matrix, which allows exosomes, independent of their origin from poorly or highly metastatic cells, to modulate (pre) metastatic organ cells for tumor cell embedding and growth.

Time course microarray data consist of mRNA expression from a common set of genes collected at different time points. Such data are thought to reflect underlying biological processes developing over time. In this article, we propose a model that allows us to examine differential expression and gene network relationships using time course microarray data. We model each gene-expression profile as a random functional transformation of the scale, amplitude, and phase of a common curve. Inferences about the gene-specific amplitude parameters allow us to examine differential gene expression. Inferences about measures of functional similarity based on estimated time-transformation functions allow us to examine gene networks while accounting for features of the gene-expression profiles. We discuss applications to simulated data as well as to microarray data on prostate cancer progression.

We describe the realization of an atomic force microscope architecture designed to perform customizable experiments in a flexible and automatic way. Novel technological contributions are given by the software implementation platform (RTAI-LINUX), which is free and open source, and from a functional point of view, by the implementation of hard real-time control algorithms. Some other technical solutions such as a new way to estimate the optical lever constant are described as well. The adoption of this architecture provides many degrees of freedom in the device behavior and, furthermore, allows one to obtain a flexible experimental instrument at a relatively low cost. In particular, we show how such a system has been employed to obtain measures in sophisticated single-molecule force spectroscopy experiments [Fernandez and Li, Science 303, 1674 (2004)]. Experimental results on proteins already studied using the same methodologies are provided in order to show the reliability of the measure system.

Tumor microenvironment is enriched in plasma membrane microvesicles (MV) shed from all cell types that constitute the tumor mass, reflecting the antigenic profile of the cells they originate from. Fibroblasts and tumor cells mutually communicate within tumor microenvironment. Recent evidences suggest that tumor-derived MVs (TMV) exert a broad array of biological functions in cell-to-cell communication. To elucidate their role in cancer-to-fibroblast cell communication, TMV obtained from two prostate carcinoma cell lines with high and weak metastatic potential (PC3 and LnCaP, respectively) have been characterized. TMV exhibit matrix metalloproteinases (MMP) and extracellular MMP inducer at their surface, suggesting a role in extracellular matrix degradation. Moreover, TMV not only induce the activation of fibroblasts assessed through extracellular signal-regulated kinase 1/2 phosphorylation and MMP-9 up-regulation, increase motility and resistance to apoptosis but also promote MV shedding from activated fibroblasts able in turn to increase migration and invasion of highly metastatic PC3 cells but not LnCaP cells. PC3 cell chemotaxis seems, at least partially, dependent on membrane-bound CX3CL1/fractalkine ligand for chemokine receptor CX3CR1. The present results highlight a mechanism of mutual communication attributable not only to soluble factors but also to determinants harbored by MV, possibly contributing to the constitution of a favorable niche for cancer development.

By controlling the timing and duration of hydrogen exposure in a fixed thermal process, we tuned the diameters of carbon nanotubes (CNTs) within a vertically aligned film by a factor of 2, and tuned the areal densities by an order of magnitude. The CNT structure is correlated with the catalyst morphology, suggesting that while chemical reduction of the catalyst layer is required for growth, prolonged H2 exposure not only reduces the iron oxide and enables agglomeration of the Fe film, but also leads to catalyst coarsening. Control of this coarsening process allows tuning of CNT characteristics.

Objective: To determine whether levels of B cell activating factor (BAFF), a member of the tumor necrosis factor family, relate to autoantibody levels, disease activity, and response to treatment in patients with early rheumatoid arthritis (ERA)., Methods: BAFF was measured by ELISA in 48 early RA patients; 21 were examined serially. These data were compared with 49 controls with longstanding RA (LSRA), 48 disease controls (DC), and 50 healthy controls (HC)., Results: BAFF levels were higher in ERA, compared with DC and HC [median 4.3 ng/ml (5th-95th: 0.8-38.8) vs 0.9 ng/ml (5th-95th: 0.7-4.5) and 2.0 ng/ml (5th-95th: 0.7-5.68), respectively; p <10(-4 )both comparisons], but not with LSRA controls [median 8.7 ng/ml (5th-95th: 0.8-46.1); p = nonsignificant]. BAFF correlated with the titers of IgM rheumatoid factor and anti-cyclic citrullinated peptide autoantibody (r = 0.76 and r = 0.49; p < 0.00001, p = 0.0001 for the 2 correlations), and with the number of swollen joints (r = 0.37; p = 0.01). The followup study of 21 methotrexate-treated ERA patients revealed reduced levels of BAFF, with parallel improvement in clinical activity and decrease in autoantibody titers., Conclusion: Elevated BAFF in a subset of ERA patients is related to autoantibody levels and synovitis. BAFF level diminished with treatment, along with autoantibody titers, suggesting a rationale to treat ERA patients with BAFF-targeted agents.

Purpose: Gleason sum 7 prostate cancers are a heterogeneous group with diverse tumor behaviors and disease outcomes. Tertiary Gleason patterns are reported with increasing frequency, particularly in prostatectomy pathology reports. We studied the pathological and biochemical outcome following radical prostatectomy in men with Gleason sum 7 and tertiary Gleason pattern 5., Materials and Methods: We reviewed 1,110 cases of clinically localized prostate cancer treated with primary radical prostatectomy between January 1998 and August 2006 through a prospectively collected prostate cancer database. Patients who underwent neoadjuvant or adjuvant hormonal deprivation, radiation or systemic chemotherapy were excluded., Results: Of the 1,110 patients 509 had Gleason sum 7 cancer. Tertiary Gleason pattern was present in 66 of 509 cases (13%) and it was absent in 443 (87%). On multivariate analysis tertiary Gleason pattern 5 was associated with higher pT stage (OR 2.55, 95% CI 1.40-4.65) and biochemical recurrence (HR 1.78, 95% CI 1.00-3.17). On subgroup analysis when patients with Gleason sum 3 + 4 + 5 and 4 + 3 + 5 were compared to their respective referent groups without the tertiary Gleason pattern, the 2 groups showed a trend toward higher pathological stage and prostate specific antigen progression. Patients with Gleason sum 3 + 4 with no tertiary pattern had higher PSA recurrence-free probability than those with Gleason sum 3 + 4 + 5 or 4 + 3 and patients with Gleason sum 4 + 3 + 5 had the lowest PSA recurrence-free probability., Conclusions: In patients with Gleason sum 7 prostate cancer tertiary Gleason grade 5 is significantly associated with higher pT stage and biochemical recurrence. Larger studies are needed to assess the predictive value of tertiary grade compared to other established parameters in predicting the long-term oncological outcome after radical prostatectomy.

The introduction of the prostate-specific antigen (PSA) test has led to dramatic changes in the incidence of prostate cancer in the United States. In this article, we use information on the increase and subsequent decline in prostate cancer incidence following the adoption of PSA to estimate the lead time associated with PSA screening. The lead time is a key determinant of the likelihood of overdiagnosis, one of the main costs associated with the PSA test. Our approach conceptualizes observed incidence as the sum of the secular trend in incidence, which reflects incidence in the absence of PSA, and the excess incidence over and above the secular trend, which is a function of population screening patterns and the unknown lead time. We develop a likelihood model for the excess incidence given the secular trend and use it to estimate the mean lead time under specified distributional assumptions. We also develop a likelihood model for observed incidence and use it to simultaneously estimate the mean lead time together with a smooth secular trend. Variances and confidence intervals are estimated via a parametric bootstrap. Our results indicate an average lead time of approximately 4.59 years (95% confidence interval [3.24, 5.93]) for whites and 6.78 years [5.42, 8.20] for blacks with a corresponding secular trend estimate that is fairly flat after the introduction of PSA screening. These estimates correspond to overdiagnosis frequencies of approximately 22.7% and 34.4% for screen-detected whites and blacks, respectively. Our results provide the first glimpse of a plausible secular trend in prostate cancer incidence and suggest that, in the absence of PSA screening, disease incidence would not have continued its historic increase, rather it would have leveled off in accordance with changes in prostate patterns of care unrelated to PSA.

Purpose: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently found to predict treatment outcome in non-small cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared with primary NSCLC. In all studies FISH have been performed on histologic material. The possibility to perform FISH analysis on cytologic material obtained by fine-needle aspiration from superficial and visceral metastases would allow us to know the real EGFR status avoiding invasive diagnostic procedures., Methods: EGFR gene copy number was analyzed by FISH on fine-needle aspirates obtained from 31 patients with metastatic NSCLC and the results were compared with those obtained on corresponding paraffin histologic sections from the primary tumor., Results: The feasibility of EGFR FISH on cytology was 90% (28 of 31 patients). EGFR FISH was positive in 61% (17 of 28 patients) of the metastases and in 36% (10 of 28 patients) of the primary tumors. Nine of the 28 cases (32%) were EGFR positive on both primary tumor and metastatic site and 10 (36%) were negative on both primary tumor and metastasis. Nine of the 28 cases (32%) showed discordance of primary tumor versus metastasis (McNemar test; p = 0.041)., Conclusions: EGFR FISH can be reliably assessed on fine-needle aspirates obtained from NSCLC metastases. We found that EGFR gene copy number is discordant between primary NSCLC and the corresponding distant metastatic sites in a significant proportion of cases. These findings should be considered in future studies designed to elucidate the predictive role of EGFR FISH in NSCLC.

Previous findings have shown that the human somatosensory cortical systems that are activated by passive nonpainful electrical stimulation include the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), and bilateral insula. The present study tested the hypothesis that these areas have different sensitivities to stimulation frequency in the condition of passive stimulation. Functional MRI (fMRI) was recorded in 24 normal volunteers during nonpainful electrical median nerve stimulations at 0.5, 1, 2, and 4 Hz repetition rates in separate recording blocks in pseudorandom order. Results of the blood oxygen level-dependent (BOLD) effect showed that the contralateral SI, the bilateral SII, and the bilateral insula were active during these stimulations. As a major finding, only the contralateral SI increased its activation with the increase of the stimulus frequency at the mentioned range. The fact that nonpainful median-nerve electrical stimuli at 4 Hz induces a larger BOLD response is of interest both for basic research and clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner., (Copyright 2007 Wiley-Liss, Inc.)

Great ongoing debate still exists over the definition, diagnosis and treatment of gastrointestinal stromal tumour especially for small gastric submucosal tumours. Simple endoscopic biopsy is not sufficient to determine their biological behaviour and their complete excision is necessary. We report the case of a 65-year-old woman, who was kept under observation after previously operated breast cancer, with a casual computed tomography-diagnosed submucosal gastric lesion. Endoscopy and endoscopic ultrasound confirmed a submucosal mass of 2-3 cm in diameter. An endoscopic resection was performed and the mass was integral at pathologic examination. It confirmed the stromal origin with a mitotic index of 1 (5/50 high power field). No more treatment was carried out because it was classified as a very low risk gastrointestinal stromal tumour according to Fletcher's classification. After 34 months follow-up, the patient is disease free and we believe that endoscopic treatment is sufficient and recommended for mainly intragastric growing gastrointestinal stromal tumour with a diameter of less than 3 cm.

Objectives: To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy., Patients and Methods: We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR)., Results: None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy., Conclusions: The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.

Overexpansion techniques are useful in overcoming a shortage of donor site for expansion: the aim of the authors was to verify whether this technique should be chosen instead of serial expansions for creation of wider and more malleable flaps for reconstruction. From 1993 to May 2005 we have overexpanded 59 patients with burn scars. The patients always underwent reconstruction at least 2 years after complete healing. Almost any body region capable of expansion has been overexpanded. The technique is illustrated here in the reconstruction of scalp, neck, trunk and thigh. Tissue expander original volume ranged from 450 to 800 cc: the silicon implant shape was both round and rectangular. Mean overinflation was 3.6 times beyond the stated vendor's maximum volume. The principle ratios were performed in the trunk (4.375) and in the lower extremities (4.125). The largest volume instilled in a single tissue expander was 3,500 cc. Overall expansion length was on average 172.6 days (range: 101-248). All patients were compliant with inflation once a week. The reconstructions were planned as the expansion of a transposition or an advancement flap. All patients had completion of their reconstruction with satisfactory resolution of their problem: complications occurred in three of all hyperinflated prostheses. Tissue overexpansion, if carefully planned and conducted, allows the completion of reconstruction in one-stage. Instead of serial expansions, it enhances patient compliance and reduces cost.

The possibility of accidental contamination of a suspect by gunshot residues (GSRs) is considered. If two hypotheses are taken into account ("the suspect has shot a firearm" and "the suspect has not shot a firearm"), the likelihood ratio of the conditional probabilities of finding a number n of GSRs is defined. Choosing two Poisson distributions, the parameter lambda of the first one coincides with the mean number of GSRs that can be found on a firearm shooter, while the parameter mu of the second one is the mean number of GSRs that can be found on a nonshooter. In this scenario, the likelihood ratio of the conditional probabilities of finding a number n of GSRs in the two hypotheses can be easily calculated. The evaluation of the two parameters lambda and mu and of the goodness of the two probability distributions is performed by using different sets of data: "exclusive" lead-antimony-barium GSRs have been detected in two populations of 31 and 28 police officers at diverse fixed times since firearm practice, and in a population of 81 police officers who stated that they had not handled firearms for almost 1 month. The results show that the Poisson distributions well fit the data for both shooters and nonshooters, and that the probability of detection of two or more GSRs is normally greater if the suspect has shot firearms.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been shown to cause typical cystic fibrosis (CF) and several milder phenotypes. We report on two asymptomatic sisters who had isolated increased sweat chloride concentrations, and in whom systematic scanning of the whole coding region of the CFTR gene revealed the F508del/S1455X genotype., ((c) 2005 Wiley-Liss, Inc.)

Aims and Background: Taxanes are largely metabolized and almost exclusively excreted in the feces by the liver through the biliary pathway, thus providing a rationale for investigating the activity of their hepatic artery delivery in case of liver metastases., Study Design: The aim of this study was to assess the feasibility of administering docetaxel via the hepatic artery in advanced breast cancer patients in whom the liver was the only or the predominant site of metastatic involvement. The dose was increased cycle by cycle in a prospective manner., Results: Ten eligible patients were enrolled. The median administered dose in the last cycle was 65 mg/m2 (range, 40-100 mg/m2). The treatment was generally well tolerated, and only one patient stopped after two cycles because of toxicity. Four of the 9 eligible patients with assessable liver tumors achieved an objective response. After a median follow-up of 41 months, 4 of the 10 eligible (and 11 treated) patients were alive with a median overall survival of 46 months., Conclusions: The administration of docetaxel via the hepatic artery is feasible. The highly interesting response and survival results observed in this limited series of patients warrant further studies.

Functional magnetic resonance imaging (fMRI) was used to study the cortical activity of the bilateral secondary somatosensory cortex (SII) during nonpainful (motor threshold) and painful electrical stimulation of median and tibial nerves. fMRI recordings were performed in eight normal young adults. The aim was at evaluating the working hypothesis of a spatial segregation of nonpainful and painful populations not only in the "hand" representation of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study. NeuroImage 20, 1625-1638.] but also in its "foot" representation. Results showed that, in both "hand" and "foot" representations of bilateral SII, the activity elicited by the painful stimulation was localized more posteriorly with respect to that elicited by the nonpainful stimulation. A fine spatial analysis of the SII responses revealed a clear somatotopic organization in the bilateral SII subregion especially reactive to the nonpainful stimuli (i.e., segregation of the hand and foot representations). In contrast, it was not possible to disentangle the "hand" and "foot" representations of SII for painful stimuli. These results extended to the SII "foot" representation previous evidence of a spatial segregation in the SII "hand" representation of subregions for the painful and nonpainful stimuli. Furthermore, they suggest that noxious information is not somatotopically represented in human bilateral SII, at least as inferred from fMRI data at 1.5 T.

The possibility of detection of lead-antimony-barium aggregates from non-firearm sources is confirmed according to the tests performed on brake pads, and firework and automobile workers. Moreover, information on particles taken from cartridge cases shows the relative feeble importance of the morphology in distinguishing gunshot residues (GSRs). Furthermore, also the presence in the spectrum of other elements (e.g., iron) is not so conclusive. In this panorama, the possibility of discriminating gunshot residue particles from other non-firearm lead-antimony-barium aggregates is investigated: the proposed method is based on X-ray mapping technique--currently applied used in Reparto Carabinieri Investigazioni Scientifiche in Rome, the forensic service of Italian Carabinieri--according to which the spatial distribution of the emission energy of each element of the sample is pictured. Gunshot residues present the same lead-antimony-barium distribution (or at least the same antimony-barium distribution with lead nodules), as some other environmental occupational aggregates do not (different plaques of lead, antimony, and barium). So, X-ray mapping technique can offer a new fundamental evaluation parameter in analysis of gunshot residues with scanning electron microscopy/energy-dispersive (SEM/EDS) spectrometry, and new standards could be considered.

We report on a 10-month-old boy with hypotonic dehydration and metabolic alkalosis. Sweat test was borderline and genetic analysis was negative for common mutations. Analysis of the whole coding regions of the CFTR gene revealed the rare mutation D579G in homozygosity.

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

Background: A useful reconstructive tool, as a delayed method, for marginal defects of the ear of more than 2.5 cm wide with no deficit of the cartilaginous frame and low scapha involvement, consists of tubed flaps raised from neighboring areas. The patients treated with this technique sustained a dog bite in three cases, a human bite in one case, a motorcycle accident in one case, and finally, a burn trauma in two cases., Objective: Three different cases of acquired marginal defects, namely ascending superior helix, descending helix, and cauda elicis with lobule involvement, are shown., Methods: In the helix reconstruction, the tube width has not to be more than 15 mm, and the tube length has to be 1 cm longer than the defect. There was no conditioning of the flaps. No pedicle bridge was interposed along the major tube. The interval between two divisions was on average approximately 5 weeks., Results: Seven patients were treated with this technique: In all cases, we had no infections or skin necrosis. To avoid a shrinkage of the tube, a correct ratio between flap dimensions and helical defect has to be estimated., Conclusion: Although it is considered an old technique and it is a multistage reconstructive sequence, this procedure could be the first preference in cases of marginal defects more than 2.5 cm wide. This is because it restores naturally the anatomy of the helix.

Background: The international literature describes many different techniques for correcting prominent ears. Some of these techniques use weakening of the anterior surface in an "open or close" way. Others use suturing of the unfold antihelix. Still others suture the concha with mastoid, and some combine several of these procedures. There is thus no most widely accepted single method. Since 1993, the senior author has used the described technique on a group of 40 patients (35 bilateral and 5 monolateral cases). Before 1993, the senior author always used an "open" technique, but the anterior cartilage was weakened by the partial parallel incision procedure., Methods: In the current study, the surgical approach for cases with a normal or moderately deep concha consisted of open anterior otoplasty with cartilage abrasion by an electric burr alone. If the concha was severely hypertrophied, concha-mastoid suturing was combined with otoabrasion, as previously described., Results: The follow-up period was a minimum of 16 months and a maximum of 8 years. Complications were rare and rapidly resolved. The outcome was successful whether the burr alone or a combined method was used., Conclusions: The authors believe that anterior abrasion of ear cartilage is a useful, simple technique that is not too time consuming by which an immediate postoperative aesthetic improvement is reached. It also is more precise and safe than the partial parallel incision procedure.

Two rare cases of mechanical intestinal obstruction due to an omphalomesenteric duct remnant and/or to a Meckel's diverticulum, respectively, are reported. The first case was a 20-year-old man and the second an 87-year-old woman. In contrast with various reports in the literature, our experience demonstrates that this kind of obstruction may also affect elderly female patients in western countries. Both patients showed signs and symptoms of intestinal obstruction and were operated on as emergencies. A complete diagnosis was possible only at operation and early surgery was important to prevent strangulation and gangrene of the bowel. The authors conclude that prompt and appropriate surgical treatment reduces the mortality risk in all patients with intestinal obstruction, including even resected cases.

The ingestion of probiotics is associated with various beneficial effects on human health and modifies the physiological homeostasis of the intestinal flora. Probiotics are microorganisms with some particular characteristics: human origin, safety in human use, bile and acid resistance, survival in the intestine, at least temporary colonization of the human gut, adhesion to the mucosa and bacteriocine production. Thanks to these characteristics, probiotics block the invasion of human intestinal cells by the enteroinvasive bacteria. Furthermore, they should be able to stimulate and modulate the intestinal immune response, and to protect and stabilize the mucosal barrier. Finally, the efficacy of probiotics should be evident and documented with valid studies. All their properties should be maintained during processing and storage. Probiotics are usually used to protect the host from pathogens. With regard to this, they are useful in the prevention of antibiotic and traveler's diarrhea and they may play a role in the management of gastric Helicobacter pylori infection. Furthermore, their efficacy in the treatment of infectious diarrhea, in inflammatory bowel diseases, in pouchitis and in food allergy has been shown. Probiotics can improve the symptoms of irritable bowel syndrome and of lactose malabsorption. Finally, it has been suggested that such microorganisms may play a role in the prevention of carcinogenesis and of tumor growth.

Sleep-related oxygen desaturation has been described in patients with cystic fibrosis (CF). Thus we studied the effects of inhaled Salmeterol xinafoate, a long-acting beta-2 agonist, on transcutaneous oxyhemoglobin saturation in sleeping, stable CF patients. Patients with stable CF (n = 23) were divided into responders and nonresponders to beta-2 agonists, based on an albuterol challenge during daytime testing, and then they received salmeterol before sleep, in a double-blind crossover design. Overnight oxyhemoglobin saturation measurements and spirometry on awakening were performed. Salmeterol administration before sleep resulted in statistically significant increases in mean arterial oxyhemoglobin saturation and in FEV(1) and FEF(25-75) on awakening compared to placebo values, but only in patients responding to daytime albuterol inhalation by showing improvement in lung function. We conclude that salmeterol inhalation at bedtime could prevent or reduce nocturnal hypoxemia in daytime albuterol-responsive CF patients, thus improving the long-term clinical outcome of CF lung disease., (Copyright 2002 Wiley-Liss, Inc.)

Diverticular disease is prevalently only of medical interest. Repeated episodes of diverticulitis, particularly in younger patients, and serious complications such as perforation, stenosis, fistula and haemorrhage demand surgical treatment. The timing and type of surgical operation are conditioned by the pathological picture and by the patient's general condition and age. The authors present a series of 586 patients admitted for diverticular disease, 84 of whom presented complicated diverticulosis. Nineteen cases (22.6%) underwent elective surgery in the form of an anterior rectal resection, while 65 of them underwent urgent surgery for complicated diverticulosis variously consisting in total colectomy, a Hartman's resection, a simple rectal resection or a left or right hemicolectomy.

To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug.