European Review for Medical and Pharmacological Sciences

Caudal anesthesia is widely used as intraoperative and postoperative analgesia in children's subumbilical surgeries such as on the urogenital system, lower extremities and lower abdomen to reduce the stress response to surgery and to facilitate the general anesthesia. The purpose of this study was to compare the effects of caudally administered bupivacaine and levobupivacaine of equal volume and concentration on motor block and postoperative pain in children undergoing circumcision surgery. The prospective, randomized, double-blind study included 60 patients with ages ranging from 1-10 years and ASA (American Society of Anesthesiologists) physical status of I-II who underwent elective circumcision surgery. The patients were divided into two groups: group B received 0.5 ml/kg of bupivacaine 0.25% caudally and group L received 0.5 ml/kg of levobupivacaine 0.25% caudally. Postoperative pain was assessed by children's and infant's postoperative pain scale and motor block was assessed by the Bromage scale. The mean children's and infant's postoperative pain scale of group B was significantly lower than that of group L (p < 0.001). Three patients in group B and seven patients in group L needed additional analgesia after the incision. There was no significant difference between groups in terms of Bromage scores and in both groups the residual motor block was found to be zero at the 150th minutes. According to these findings, bupivacaine has an adequate quality of analgesia than levobupivacaine. We suggest that bupivacaine for caudal block at the concentration of 0.25% (0.5 ml/kg) provides an adequate level of analgesia for outpatient circumcision surgery.
Time course of the Hollmen simplified scale in the two groups (open circles = Group L 0.25 and closed squares = Group contrl ). Two-ways ANOVA: p < .01; post-hoc Fisher exact test: °p < 0.05 Group CONTROL vs Group L 0.25 ).  
Time course of the Bromage scale (open circles = Group L 0.25 and closed squares = Group CONTROL ). Twoways ANOVA: p < .01; post-hoc Fisher exact test: p < .05 Group control vs Group L 0.25 ).  
Time course of Blood pressure mean (open circles = Group L 0.25 and closed squares = Group control ). Twoways ANOVA: p < .01; post-hoc Fisher exact test: p < .05 Group L 0.50 vs Group L 0.25 ).  
In spinal anaesthesia for a Caesarean delivery, it is important to limit anaesthesia only at the surgical area, and to resolve fast motor block. We compared the intraoperative effectiveness, hemodynamic effects, anaesthetic recovery times and patients satisfaction after isobaric levobupivacaine (L) 0.25% versus L0.50% spinal anaesthesia during elective Caesarean deliveries performed with the Stark technique. In this double-blinded prospective study, seventy women undergoing elective caesarean delivery were randomized to receive either intrathecal 7.5 mg Levobupivacaine 0.25% plus sufentanil 2.5 μg (Group L0.25), or intrathecal 7.5 mg L 0.50% plus sufentanil 2.5 μg (GroupControl). The onset time, duration of anaesthesia, analgesia and sensory and motor block and hemodynamic parameters were measured from the beginning of spinal anaesthesia until four hours after spinal anaesthesia (T240). Onset time, duration of anaesthesia and haemodynamic variations were similar in the two groups. No patients required general anesthesia to complete surgery. Motor block vanished faster in Group L0.25 as compared with GroupControl (p < .01). The cephalad spread of the 0.50% solution was higher than that of the 0.25% solution: no patient in Group L0.25 experienced paresthesia of the upper limbs vs 14% in GroupControl (p < .05). In GroupControl anaesthesia reached the dermatome T1 in 15% of cases. Maternal and surgeon satisfaction was good in every patient. Levobupivacaine 7.5 milligrams at 0.25% may be used as a suitable alternative to L 0.50% for spinal anaesthesia for caesarean deliveris with the Stark technique with good maternal satisfaction. In Group L0.25 a lower appearance of nausea and hypotension were observed and motor and sensitive block developed and diminished faster while no clinically significant differences in hemodynamic behavior was observed between groups.
Mean tonometric values in a twice daily Timolol 50% therapy before and after replacement with the fixed combination Latanoprost-Timolol one daily. (Checkup at 1, 3, 6, 12 and 24 months from the beginning of the treatment). IOP: intraocular pressure. 
Average tonometric values in twice daily 0.50% Timolol therapy associated with once daily Latanoprost before and after replacement with the fixed once daily Latanoprost-Timolol combination. (Checkup at 1, 3, 6, 12 and 24 months). IOP: intraocular pressure. 
To evaluate the ocular hypotensive effects and tolerability of the once daily fixed combination latanoprost-timolol versus twice daily 0.50% timolol associated or not with once daily latanoprost in patients suffering from Primary Open-Angle Glaucoma (POAG). We compared the effects of such a combination with those of 0.50% timolol alone twice daily in a group of 24 patients and with the effects of timolol 0.50% twice daily associated with once daily latanoprost in a second group of 20 patients with a follow-up of 24 months. In the first group of patients after one month the Intraocular Pressure (IOP) was reduced from a mean of 19.93 to a 17.04 mmHg. This reduction remained stable with a mean value of 17.00 mmHg at the third month, of 16.49 mmHg at the sixth month, of 17.04 at the twelfth month, 16.00 at the eighteenth month, and of 15.86 mmHg in the twenty-fourth month. In the second group there was a statistically significant reduction from 19.4 to 16.84 mmHg after one month. This reduction remained constant with mean values of 16.47 at the sixth month, of 16.20 at the twelfth month and of 16.00 mmHg at the twentyfourth month of treatment. The once daily latanoprost-timolol combination was shown to furtherly reduce the Intraocular Pressure (IOP) (p=0.001) and to maintain under control the intraocular pressure for the observation period (24 months). Both topical and systemic side-effects were scarse and tolerability was good.
The aim of this prospective study was to evaluate the prevalence of allergic asthma and or rhinitis (AR) in 1182 children. Systemic reactions (SRs) to asthma desensitization, previously, specific immunotherapy (SIT) in children with allergic asthma and or AR are scarcely known. Since 1999, we have consecutively enrolled all children ranging in age from 3 to 11 years attending our Division because affected with severe asthma (592). Controls were 590 nonatopic children matched for age and sex recruited from our outpatient clinic. The study children were treated with a personalized asthma desensitization, the controls were treated with all usual medications. The parents of all children gave their informed consent. Data were analyzed using the X2 method. The 592 atopic children with severe asthma, 370 males and 222 females, aged 3.5 to 10.5 years, tested positive for Der p and Der f (47.1%) or for pollen allergens (52.9%). We have demonstrated a high increase of ashma incidence, since at the start there were 135 asthmatic children and 215 during 2000, with a 62.5% increase. During 2001 there were 242 children, with a 88.8% increase compared to 1999. All of these children were subjected to asthma desensitization, previously SIT (SARM, Roma). At the third yearly control, the study children had a significantly greater reduction as regards days (p = 0.0001) and nights (p = 0.0005) without asthma and drug usage (p = 0.0003) compared with drug-treated children. The number of SPTs and/or sigE to inhalants also decreased, spirometry data were also notably improved The clinically adverse events only were mild or transient. The positive results obtained in this large study add to its safety in our opinion because the children were followed by their doctors also on the basis of "as frequently as needed". Accordingly, the early onset of childhood asthma emphasizes that an early treatment is the only means to significantly abate the march of atopic asthma. We have documented an unexpected prevalence of pediatric asthma that should by evaluated in light of the very early asthma development in children which is present even before asthma would be diagnosed based on clinical symptoms The causes of this dramatic increment (10.4%/month in the last six months) may be identified chiefly in the worldwide increase in air pollution and secondhand tobacco smoke.
Vascularized bone-grafting pedicled on 1,2 intercompartmental supraretinacular artery (1,2 ICSRA) has been recommended as a treatment alternative for established scaphoid nonunion complicated with proximal pole avascular necrosis (AVN). Previous reports focused the studies on the union rate and the revascularization of the transferred graft. However, the postoperative wrist stiffness still a challenging problem and remaining to be solved. The purpose of our study was to determine whether the combination of vascularized bone-grafting pedicled on 1,2 ICSRA and wrist external fixator immobilization provides a more effective strategy for treating established scaphoid nonunion complicated with AVN and improving postoperative range of motion (ROM) of the injured wrist. We retrospectively reviewed a consecutive series of 11 patients who had cases of established scaphoid nonunion involving AVN of the proximal pole were treated with vascularized bone-grafting pedicled on 1,2 1,2 ICSRA, internal fixation, and wrist external fixator immobilization. Procedure of wrist arthrolysis was performed before vascularized bone graft transferring. Preoperative and postoperative evaluation included measurement of clinical (wrist ROM and grip strength), radiographic (intrascaphoid angle, scapholunate angle) and functional (Mayo wrist score) parameters. Osseous union was achieved in all of the 11 cases within an average period of 11.4 weeks. On an average 6.1 years follow-up, there were three excellent, six good and two fair results. Significant improvements were found for Mayo wrist score, wrist ROM, and grip strength (p < 0.01). Intrascaphoid angle and scapholunate angle were significantly improved postoperatively, and there was no significant difference between the postoperative values and the values at the last follow-up. Early functional rehabilitation of the injured wrist under the protection of the fixator did not result in displacement of the transferred graft. The results of the present investigation support the use of the vascularized bone graft pedicled on 1,2 ICSRA in the treatment of scaphoid nonunion complicated with proximal pole AVN. Procedures of wrist arthrolysis and early institution of wrist functional rehabilitation under the protection of the external fixator play important role in the restoration of range of motion of the injured wrist.
We tested the hypothesis that curcumin, a polyphenolic antioxidant, acts as a powerful free radical scavenger in vivo in the brain, and interferes with oxidative stress caused by the parkinsonian neurotoxin, (MPTP) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We measured the (GSH) reduced glutathione levels, (TBARS) glutathione lipid peroxidation, (CAT) catalase and (SOD) superoxide dismutase activity in the (ST) striatum and (MB) mid brain 3rd day and 7th day following MPTP and curcumin administration. MPTP treatment caused a significant depletion in GSH and increased the specific activity of SOD, CAT and lipid peroxidation in both ST and MB on the 3rd and 7th day. MPTP induced GSH depletion and lipid peroxidation in ST and MB was blocked by curcumin treatment. Curcumin exhibited a synergistic effect on SOD and CAT activities in the ST and MB regions. The present study provides direct evidence for the involvement of curcumin in neuroprotection against oxidative stress.
Curcumin exhibits growth-suppressive activity against a variety of cancer cells, but low bioavailability prevents its use in chemotherapeutic applications. One strategy for circumventing this problem has been the creation of synthetic analogs. In this study we synthesized an analog of curcumin bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) and investigated its anti-breast cancer property. We compared the impact of bis-1,7-2(hydroxyphenil)-hepta-1,6diene-3,5diore (BDMC-A) with that of curcumin in human breast cancer cell line MCF-7. MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] cell viability assay was used to examine the cell viability/proliferation. LDH assay and cell counts were performed to assess the cytotoxicity and anti-proliferative effects of the compound respectively. Flow cytometry followed by Western blot were performed to investigate the cell cycle distribution. BDMC-A has an inhibitory effect on MCF-7 cells comparably equivalent to that of curcumin as determined by MTT assay. Cytotoxicity of the cells by both curcumin and BDMC-A were confirmed by LDH release assay and cell count assay. Flow cytometric studies showed accumulation of cells in the G2/M phase which confirms the cell cycle arrest. This was further confirmed by immunoblotting of the protein Cyclin D1, whose expression were found to be decreased in both curcumin and BDMC-A treatment. The results indicate that the curcumin analog exhibit potent inhibitory activity which is comparable to that of curcumin in human breast cancer cells. Since the solubility of BDMC-A was higher in aqueous medium, it is expected to be more bioavailable, and hence more active in vivo. Further evaluation might reveal its role on various molecular targets.
tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints, without affecting endometrial thickness and lipid profile or blood glucose. However, the potentially similar efficacy, but better tolerability, of a low dose of this drug (1.25 mg) has never been established. 162 healthy, non-obese, post-menopausal women, aged 40-65 years, with an intact uterus were enrolled in a national, single centre, randomised, double blind, placebo controlled, parallel group trial. After 1 week of runin, patients were treated for 24 weeks with placebo, tibolone 1.25 mg or 2.5 mg/day. During the study laboratory tests, endometrial ultrasound scans and mammography were performed. Occurrence of menopausal signs and symptoms, including vaginal bleeding, and quality of sexual life were also checked. in the 120 patients terminating the study without major protocol violations, climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg (78% and 90% reduction at week 24 for hot flushes, 36% and 34% for sweating episodes and 44% and 51% for vaginal dryness), but not by placebo. Benefits occurred earlier in the group treated with tibolone 2.5 mg. Quality of sexual life was almost invariably improved by tibolone as compared to placebo, but improvement occurred earlier in the tibolone 1.25 mg group. Severity of vaginal bleeding was not different between placebo and active treatment groups, except at week 12 when was higher. At the end of treatment vaginal bleeding occurred in 15% of patients treated with placebo, 14% treated with tibolone 1.25 mg and 12% treated with tibolone 2.5 mg. Endometrial thickness and breast density were not changed by treatment, as well as FSH, 17-beta-estradiol, total cholesterol, HDL and LDL cholesterol, triglycerides and blood glucose. Adverse events were reported by 14.7%, 26.7% and 24.4% of patients treated with placebo, tibolone 1.25 mg and tibolone 2.5 mg/day, respectively. tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles, though were more effective than placebo. Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function.
Red cell distribution width (RDW) is associated with poor cardiovascular outcomes. We aimed to find out if this association could be explained by impaired exercise capacity in patients without obstructive coronary artery disease (CAD). The patients who underwent exercise treadmill test (ETT) who have non-obstructive CAD and were free of heart failure symptoms were evaluated. Total of 132 patients were enrolled, and patients were divided into three groups according to their Metabolic Equivalent Task (MET) level measured by exercise treadmill test (ETT): Less than 7 METs (group 1), 7-10 METs (group 2) and greater than 10 METs (group 3). The patients in Group 1 had significantly higher RDW levels (16.46 ± 2.79) compared to Group 2 (15.05 ± 2.03) and Group 3 (14.52 ± 1.37), independent of hemoglobin and hematocrit values. Significant differences for age, gender, duration of ETT and Duke Treadmill Score were also found in proportion to the reduced exercise capacity. In multivariate analysis, only duration of ETT (β = 1.017, p = < 0.001) and RDW (β = 0.040, p = 0.026) were found as independent variables, which had statistically significant effects on METs. We found an independent association between RDW and exercise capacity in patients free of obstructive coronary disease suggesting that patients with elevated RDW values are expected to have impaired exercise capacity.
Traditional treatment for uveal melanoma is the enucleation of the eye with outcomes cosmetically unacceptable and loss of useful vision. Plaque brachytherapy, compared to enucleation, had the advantage to preserve the eye with outcomes cosmetically acceptable and preservation of vision. From July 1990 to December 2009 one hundred forty-two (142) patients (51 males and 91 females) with small to medium uveal melanoma were treated with 106Ru plaque brachytherapy. The patients underwent a complete staging before brachytherapy with indirect ophthalmoscopy and ultrasounds. Mean tumour thickness was 3.26 mm (1.6-6 mm). The dose scheduled was 80-100 Gy to the apex with a maximum dose of 800 Gy to the sclera. One hundred forty-two have been treated, nine patients had lost the follow-up and drop out; 133 patients were assessed. Mean follow-up was 7.7 years (6 months-18 years). The overall survival at 5, 10 and 15 years was 92%, 85% and 78% respectively. Cancer fee survival was 95%, 90% and 83%, respectively at 5, 10 and 15 year. Radiation-induced toxicity was represented in 47 patients with a 5 year actuarial survival rate free from complications of 54%. 106Ru plaque brachytherapy is a valid approach for treatment of uveal melanoma. This technique is efficacy and safe, with a low toxicity profile.
Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, has been reported to have the ability of influencing the invasion of human cancer cells. However, the mechanisms are not very clear. In this study, we investigated the effects of propofol on the proliferation, invasion and angiogenesis of human Eca-109 cells, and explored the mechanism. The human Eca-109 cells was treated with propofol at the concentrations of 10-100 µmol/L for 72 hours or at the concentration of 100 µmol for 8-72 hours. Cell viability was determined by the MTT assay; the effect of propofol on apoptosis by 5'-triphosphate-biotin nick end labeling (TUNEL) staining. The effect of propofol on angiogenesis was determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The effect of propofol on cell invasion using a modified Matrigel Boyden chamber assay. ERK1/2, MMP-9 and VEGF leves was detected by western blotting assay. In human Eca-109 cells, propofol significantly promoted cell apoptosis and inhibited proliferation in a dose and time-dependent manner. Furthermore, propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol significantly dose and time-dependently down-regulated gene expression and protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP-9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9 signaling pathways. It was noteworthy that the ERK activator (phorbol 12-myristate 13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after propofol treatment, and led to significant increase of proliferation, invasion and angiogenesis. These findings indicate that propofol inhibited proliferation, invasion and angiogenesis of human Eca-109 cells in vitro through modulation of ERK-VEGF /MMP-9 signaling. Propofol not only can be an anesthesia agent which reduces pain but plays an important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.
To compare the effects of the pretreatment and treatment with recombinant human interleukin-11 (rhIL-11) on acute liver failure induced by D-galactosamine (D-GalN). The Sprague Dawley (SD) male rats were randomly divided into five groups: control, model, pretreatment, treatment and repeated treatment groups. The acute liver failure model was established by intraperitoneal injections with D-GalN (1400 mg/kg). The pretreatment, treatment and repeated treatment groups were injected subcutaneously with rhIL-11 (500 µg/kg). The rats were killed 24, 48, or 72 h after the D-GalN injection. The symptoms and survival rate of the rats were analysed. Liver injury was assessed by serum ALT and AST levels and by histological analysis. The percentage of Proliferating Cell Nuclear Antigen (PCNA+) cells in the liver tissue was evaluated by immunohistochemistry. Compared with the model group, the survival rate of the pretreatment group improved markedly, and these rats were protected from severe hepatic injury, as shown by the decreased serum ALT and AST levels and improved histological results. In the pretreatment group, the percentage of PCNA+ cells was significantly increased in the late stage. In contrast, the treatment and repeated treatment groups did not show improved survival rates or the prevention of severe hepatic injury, as shown by the absence of any decrease in the serum ALT and AST levels and the lack of any improvement in the histological results.The treatment and repeated treatment groups also have a significant increase in the percentage of PCNA+ cells in the late stage. The pretreatment with rhIL-11 can reduce acute liver failure and protect the liver. In contrast, the treatment with rhIL-11 cannot reduce acute liver failure or protect the liver.
Toxic epidermal necrolysis and Steven Johnson syndrome are rare diseases that usually follow drug-exposures. The authors present one retrospective study with their management and focus their retrospective analysis on finding prognostic factors. We reviewed charts of admitted patients from January 1995 to December 2005. Only those with an histologic-proved diagnosis were included in the study. Causative drugs, symptoms, management and outcome were recorded and analysed. We found 32 patients that met inclusion criteria. Mortality rate was 34.4% (11/32). Age, delay of referral, Total Burn Surface Area, white blood cells, creatinine, blood sodium, immunoglobulins therapy and more than two different types of blood bacterial species isolated were significantly correlated with death (p < 0.05). These data confirm prognostic factors already present in literature and find that the number of different bacterial species isolated from blood increase mortality. Further prospective studies are necessary to confirm these findings.
Respiratory tract infections due to viral etiology were studied with an objective to identify and compare the pathogens between Hospital Indoor and Outdoor Units. A hospital-based cross-sectional study was conducted among children below 12 years over a period of one year. The throat and nasal swabs were collected from both the Units and screened for viral infections by real time RT-PCR technique. Out of 880 samples collected, 87% and 13% were from outdoor and indoor Department with total viral positivity rate of 30% and 25% respectively. Influenza B virus (IBV) (n=126, 16%) was more prevalent in Outdoor Unit, whereas respiratory syncytial virus (RSV) (n=18, 16%) among indoor admitted cases. The multinomial logistic regression analysis revealed that both RSV and Influenza viruses were predominant in children of pre-school age groups < 5 years. In the year 2010-11, the prevalence of human metapneumovirus (HMPV) was low. The pandemic influenza A virus (pH1N1/2009) accounted for 4% (n=29) and 0.8% (n=1) cases among Outdoor and Indoor Units respectively. The Outdoor Department outnumbered the Indoor Unit in terms of patient attendees and the rate of viral infections. An effective vaccination and continuous surveillance program is the need of the hour.
Radio-guided Surgery: the used tool was Neo 2000-model 2200. 
Radio-guided Surgery: the hand-held gamma probe. 
A hilar hot area corresponding with a thickening of the upper lobar bronchus wall (target/normal tissue count ratio was 31,36). 
A correct intra-operative detection of the tumour and, therefore, the complete surgical resection is critical to success in ACTH-secreting bronchial carcinoids. To date, all available preoperative and intra-operative procedures remain not entirely satisfactory. The use of intra-operative 111In-pentetreotide detection could offer a potentially reliable and rapid tool of real time assessment to achieve a radical resection. In two cases of ACTH-secreting bronchial carcinoids, after a preliminary 111In-pentetreotide scan, radio-guided surgery was performed using a hand-held gamma probe 24 h after i.v. administration of the tracer. The 111n-pentetreotide radioguided surgery with hand-held gamma probe, if compared with pre-operative 111In-pentetreotide, significantly improved the intra-operative surgical management by detecting a millimetric nodule in one case; detecting mediastinal lymph node metastasis in both cases and ruling out any other disease localization. Intra-operative 111In-pentetreotide detection appears to be safe and easy to perform. This technique allowed to achieve a complete resection of all the tumor locations, that would have been impossible to detect with conventional surgical approach. On the basis of these results we advocate for a wider investigation of the potentialities connected with the radioguided surgery coupled with pre-operative 111In-pentetreotide scan as a promising procedure in the management of ACTH-secreting bronchial carcinoids.
Panoramic radiographs showing mesiodens in different directions. A-B, Vertical. C, Horizantal.  
To investigate the prevalence of mesiodens in a sample of Turkish dental patients and their distribution among genders. A retrospective study was performed using panoramic radiography of 11256 patients, who ranged in age from 15 to 55 years old. All data (age, sex and or syndrome) were obtained from the patient files and analyzed for mesiodens. Statistical evaluation of the presence of mesiodens related to gender was performed by the Pearson chi-squared test. Mesiodens was detected in 15 subjects (0.13%). The prevalence of mesiodens for females and males was 0.20% and 0.057%, respectively (p = 0.037). The most commonly observed mesiodens was maxillary canine-like type (60%). Most of the mesiodens (67%) were found in the vertical position, followed by horizontal position (33%). The age and sex distribution, number of mesiodens per patient, shape, direction, size, and effect on permanent maxillary incisors are also presented in this study. The most common complication caused by mesiodens was midline of the permanent incisors. Mesiodens is an uncommon developmental anomaly in Turkish dental patients. Early diagnosis allows the most appropriate treatment, often reducing the extent of surgery, orthodontic treatment and possible complications.
Cow's milk allergy (CMA) is a disease of infancy and usually appears in the first few months of life. The evaluation of infants for possible CMA is one of the more common problems shared by pediatricians. The role of foods in determining and/or aggravating the clinical features of atopic dermatitis (AD) has been stressed in the last decades. The aim of the present study was to investigate, in children with food related AD, the development of tolerance to the offending food(s), clinical or laboratory data to predict the development of food tolerance, and whether there are clinical or laboratory data to predict the onset of respiratory allergy. In this prospective study we report on 115 babies, first examined at a median age of 6 months, and followed-up for 8 years. We have investigated several factors as predictive of the outcome, as follows: early onset; widespread or not-typical (reverse pattern) skin lesions, family history positive for atopy; persisting FA, high levels of total and specific IgE antibodies, association with CMA and asthma. All these parameters were significantly predictive of a long-term morbidity of AD children with CMA. The median age for tolerance to cow's milk was 7 years + 11 months, to egg 6 years + 6 months, and to wheat 7 years + 2 months. However a great number of both tolerant and intolerant children developed multiple sensitizations. Only 66 children (57%) acquired food tolerance, but there was the onset of asthma in 54% of cases. The natural history of CMA is not well-known, since not many related studies have been done in children. The several predictive factors, all in a negative sense, may be the norm in atopic children. We suggest possible areas of intervention in children at risk due to parental atopy. Preventive measures may induce a dramatic improvement in children with food allergy, but we stress that the long-term prognosis is challenging, since asthma prevalence may increase up to 54% during a long follow-up. Therefore, the natural history of IgE-mediated AD in atopic children sensitized to several allergens may be less optimistic than generally reported.
Aim of this study was to identify the association between dermatomyositis and malignancy in China. We retrospectively analyzed the clinical data of 115 cases of dermatomyositis associated with malignancy. From 1974 to 2008, there were 678 cases of dermatomyositis collected from the Second Affiliated Hospital, Sun Yat-Sen University, China. Among them, 115 cases (17.0%) were associated with malignancy. 7.4% (22/297) of patients under 40 years old were diagnosed with malignant tumor, while 24.4% (93/381) of patients aged 40 years or above were associated with malignancy. Malignancy preceded dermatomyositis in 14 cases. Dermatomyositis and malignancy were diagnosed at the same time in 22 patients. Another 79 patients were found to have cancer within 3 years after the dermatomyositis was diagnosed. Among them, cancer was detected in 66 patients in the first year, 11 patients in the second year and only 2 patients in the third year. Nasopharyngeal cancer made up 51.3% (59/115) of the associated malignancies, while lung cancer accounted for 17.4% (20/115). Other malignancies associated with dermatomyositis included liver cancer, ovarian cancer, cervical lymph node metastases of unknown origin, cholangial cancer, esophageal cancer, colon cancer, laryngeal cancer, renal cancer, tongue cancer and lymphoma. Dermatomyositis associated with malignancy was more common in patients aged 40 years or above. Malignancy was often detected within the first year after the onset of dermatomyositis. The most common malignancy associated with dermatomyositis was nasopharyngeal cancer, followed by lung cancer in Guangdong, China.
Flow chart of the search for eligible studies on the usefulness of MIBG scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure. 
Aim: This study was designed to review published data regarding the clinical usefulness of iodine-123-meta-iodobenzyl-guanidine (MIBG) scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure (HF). Methods: A comprehensive computer literature search of the PubMed/MEDLINE and Embase databases was conducted to find relevant published articles about the clinical usefulness of MIBG scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with HF. Results: Thirty-three studies, comprising a total sample size of 1124 patients with HF, were included in this review. Main findings of the included studies are presented. Conclusions: Myocardial innervation imaging using MIBG scintigraphy can be successfully used to assess changes in cardiac sympathetic neuronal function caused by several pharmacological interventions in patients with HF.
Research literature on MIBG scintigraphy in oncology, cardiology and neurology from 1980 to 2010 (source: Pubmed/MEDLINE.  
123I-metaiodo-benzylguanidine (MIBG) scintigraphy is considered a valid imaging test to evaluate the cardiac sympathetic nervous system. However, scientific literature showed that some drugs are able to or are expected to interfere with MIBG uptake. Thirty years after introduction of the method and over 15 years since the appearance of the first document on pharmacological interference with MIBG, an update on this issue has become necessary. The aims of this review paper are: (1) to identify the pharmacological basis of interference of a variety of substances with MIBG uptake; and (2) to update the list of drugs that definitely interfere with MIBG on the grounds of evidence in the literature. A MEDLINE search was conducted. Scientific studies, case report and review articles were collected. Papers published demonstrating drugs interfering with MIBG uptake were evaluated. Drugs may interact with MIBG uptake by 5 mechanism: (1) type-1 uptake inhibition; (2) inhibition of active transport to vesicles; (3) competition in transport to vesicles; (4) depletion of neurosecretory vesicle content; (5) calcium-mediated mechanism. We find that drugs like cocaine, antidepressants, some antipsychotic, tramadol, labetalol, sympatho-mimetics, reserpine and some calcium antagonists (as diltiazem, verapamil and nifedipine) do interfere with MIBG uptake. On the other hand, we find that controversial data are available on scientific literature regarding digoxin and amiodarone. A compiled statement of MIBG interfering medicines is now recommended to help nuclear medicine physicians in clinical practice to avoid potential pitfalls and improve the efficacy of 123I-MIBG scintigraphy as a diagnostic tool.
Non-Alcoholic Fatty Liver Disease (NAFLD) is related to unhealthy habits, mainly to unfavorable dietary profiles. MTHFR gene encodes MethyleneTetraHydroFolate Reductase, a regulatory enzyme whose polymorphisms are associated with hyperhomocysteinemia. Among polymorphisms, C677T, a thermolabile form, but not A1298C, thermostable, was associated with fatty liver and insulin resistance. to investigate if NAFLD, in subjects referred for nutritional assessment and counselling, has any difference of prevalence and severity when associated with isolated MTHFR A1298C polymorphism and hyperhomocysteinemia. 94 subjects, age 55.65±15.43 years, BMI 27.88±5.17 kg/m2, 26 with MTHFR Wild type genotype (1298AA) and 68 with MTHFRA1298C single polymorphism were studied: of them, 35 were homozygous (MTHFR1298CC), 33 were heterozygous (MHTFR 1298AC). Insulin resistance was assessed by HOMA-IR, NAFLD by UltraSound Brigh-Liver-Score (BLS). MTHFR subgroups (wild and A1298C single polymorphism) were not different for age, gender, dietary profile and BMI. In NAFLD, MTHFR 1298AC (heterozygous) vs. homozygous wild genotype (MTHFR 1298AA) patients had more severe NAFLD (BLS: 1.12±1.14 vs. 0.54±0.76, p < 0.029), greater insulin resistance (HOMA 3.20±2.35 vs. 2.12±1.12; p < 0.036), higher AST and gammaGT. MTHFR1298AC gene heterozygous polymorphisms can be weakly predictive for NAFLD severity. This mutation occurs frequently in populations with low prevalence of overall mortality and of atherosclerosis-associated disease: it could have maintained and maintain its persistence by an heterozygosis advantage mechanism, within significant adherence to healthy nutritional profiles. Interactions of nutrition, genetics and health are a part of the aging process throughout the life span and a greater consideration to the genetic characteristics of populations and individuals is warranted.
Matrix metalloproteinase-13 (MMP13) is a highly regulated zinc-dependent endopeptidase and has been reported to be associated with vascular invasion and lymph node metastasis and predicts poor outcome for relatively early stage in esophageal squamous cell carcinoma (ESCC) patients. However, the role of the serum MMP-13 levels in ESCC is still unknown. In the present study, we investigate the clinical significance of MMP-13 levels in patients with ESCC. The serum level of MMP-13 was measured with commercially available ELISA kit in 112 healthy controls and 141 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and MMP-13 levels were determined using the Mann-Whitney U test. The clinical value of MMP-13 level as a prognostic parameter was evaluated using the Cox's proportional hazards model. The results showed compared with the healthy control group (74.5±12.3 ng/ml), ESCC patients tended to have significantly higher serum MMP-13 concentrations (86.2 ± 14.6 ng/ml) (p < 0.05). Elevation of MMP-13 levels (≥ 76.4 ng/ml) was observed in 61.7% (87/141) of patients with ESCC, and 18.4% (26/141) in healthy controls. MMP-13 levels were associated with lymph node metastasis (p < 0.001), distant metastasis (p < 0.001), histological differentiation (p = 0.026), T classification (p < 0.005), but not with the tumor size, clinical stage, age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of MMP-13 (≥ 76.4 ng/ml) had significantly lower 5 year survival rate than those with non-elevated MMP-13 (< 76.4 ng/ml, log-rank p < 0.001). It is suggested that the elevated level of preoperative MMP-13 was found to associate with tumor progression and poor survival in patients with ESCC.
Collagenase-3 (MMP-13), a matrix metalloproteinase, is a recently identified member of the matrix metalloproteinases (MMPs) with broad substrate specificity, and a potential role in tumor metastasis and invasion has been proposed. Collagenase-3 expression has been reported in many carcinomas. However, the presence and possible implication of MMP-13 in the progression of papillary thyroid carcinomas are unknown. In the present study, we examined MMP-13 gene expression in 208 papillary thyroid carcinomas who underwent surgery without preoperative treatment and 100 matched samples of adjacent normal thyroid tissue (Paraffin-embedded tissue samples) by immunohistochemistry analysis. In vitro and in vivo studies were done in order to investigate the effect of MMP-13 overexpression or silencing on cancer cells invasion and metastasis. We found MMP-13 expression was significantly increased in the tumours from local regional lymph node metastases patients. The MMP-13 was stained more intensely in invading fronts than in central portions of local regional lymph node. No MMP-13 staining was observed in matched samples of adjacent normal thyroid tissue. MMP-13 expression was significantly related with TNM and recurrent disease, no relation was found with age extent of tumour and size of tumour. Studies with cell and mice models indicated that overexpression of MMP-13 increased cell migration and promoted metastasis, and MMP-13 sliencing decreased cell migration. The data suggest that MMP-13 is associated with thyroid tumour invasion and metastasis and it may be a potential target for therapeutic intervention.
Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) are the result of the assumption of such drugs. The most widely used molecules are pamidronate and zoledronic acid, which are pyrophosphate analogues and are usually given to patient with bone remodelling diseases. International literature reports showed an association between this therapy and avascular necrosis, thus leading to review the guidelines for their administer. The authors present their protocol based upon medical treatment, antibiotic and antimycotic, together with minimally invasive surgery and ozone therapy developed after a 5 year experience to assess the viability of this treatment. In the last years researchers studied treatment protocols, both medical and surgical, for the management of BRONJ. Among these Ozone therapy is being adopted by several centers. From February 2004 and December 2010 a total number of 131 patients affected by BRONJ have been observed. Collected data include patients' age at the time of disorders, gender, presenting signs and symptoms, primary diagnosis, type and characteristics of the treatment performed, radiological findings and post-treatment results. At the present time there are no major guidelines in international literature for the treatment of BRONJ, the Authors then propose a therapeutic protocol based upon minimally invasive surgery, antibiotic and anti mycotic therapy with the adoption of ozone as regenerating factor for tissues. In 90% of the cases the results confirmed the procedure with successful outcomes.
Negative diagnostic 131I whole body scans with elevated serum thyroglobulin (Tg) levels are found in 20% of patients with differentiated thyroid cancer (DTC). Empirical radioiodine treatment has been advocated by some researchers, but has had with controversial outcomes. This anterospective study was performed to examine this dilemma and also to determine the capability of thallium (201TI) scintigraphy in these patients. A total of 21 patients who had a history of DTC and elevated serum Tg levels, together with a negative diagnostic 131I whole body scans (WBS), were included in the study. All patients underwent posttreatment 131I WBS. Patients with negative posttreatment 131I WBS then underwent 201TI scintigraphy. The 21 included patients (9 women and 12 men) had a mean age of 53 +/- 14.17 years. The mean pretreatment and posttreatment Tg levels were 227.23 +/- 208.50 ng/ml and 163.43 +/- 282.57 ng/ml, respectively (p value <0.05). Eleven cases showed at least a 50% decrease in Tg value (remission group), 6 patients revealed less than a 50% decrease in Tg value (stable group), while 4 subjects demonstrated an increment in posttreatment Tg relative to pretreatment Tg value (progression group). The cumulative and last 131I doses in the remission, stable, and progression groups were not significantly different (p value >0.05). In the posttreatment 131I WBS, 10 patients showed abnormal findings in their images. In a follow-up scan after 201TI treatment, 7 out of 11 patients had positive scans. The study indicates a positive effect of RAI therapy in DTC patients with elevated Tg and negative 131I WBS. In addition, 201TI scintigraphy can be useful as an alternative modality to improve tumoral detection in this situation and when access to a PET system is limited.
Microscrew inserted in the bone fragment to reduce it. 
The reduced fragments fixed with the screws. 
Frontal sinus fractures peculiarity is that a wrong treatment not only could it encompass functional or aesthetical problems but also more dangerous complications: the proximity of the frontal bone to the brain, on a side, and to the nasolacrimal duct, on the other side, and therefore to the nasal cavity, lead the traumatisms occurring within this region to be at high risk of infections. We report our experience on 132 cases of frontal sinus fracture treated from 1989 to 2005 and to present the surgical techniques performed as well as to compare the complications they reported over time to the International Literature data. 101 patients (76.5%) were treated in order to reduce and contain the isolated fractures involving the frontal sinus anterior wall, the patients presenting associated fractures of the frontal sinus anterior and posterior wall were 28 (21.2%), while the cases reporting isolated fractures of the nasolacrimal duct were 3. Our patients underwent follow-ups from 1 to 16 years long. We subdivided the complications found in our group into infectious and functional so that the incidence of the complications related to the sites and the treatment performed according to the specific case could be better assessed. In conclusion, the infectious and functional complications found were treated with a multidisciplinary study considering the approach to the craniofacial traumatized person is subordinated to the co-existence of general and neurological conditions requiring for their resolution different approaches and times.
Chronic obstructive pulmonary disease (COPD) is characterized by the presence of a low-grade systemic inflammation that is implicated in the pathogenesis of numerous extrapulmonary manifestations, such as hypogonadism. Endothelin-1 (ET-1) is a molecule that demonstrates pro-inflammatory properties and can augment the airway and systemic inflammation. Single nucleotide polymorphisms (SNPs) of the ET-1 gene that increase ET-1 serum levels are an important area of investigation. We examined the alterations in inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and in the levels of testosterone, free testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a group of male COPD smokers when compared to their age-matched controls and how these alterations relate to the presence of a functional ET-1 SNP, the adenine insertion SNP +138 insA/delA. In this case control study, 80 male control smokers and 82 male COPD smokers were recruited for comparison. Among the male COPD smokers, 37 were carriers of the +138 insA/delA SNP. Two COPD subgroups according to genotype were formed: (1) A group of 45 males homozygous for the wild type allele (3A/3A) and (2) a group of 37 males heterozygous for the mutant allele (3A/4A). Levels of testosterone and free testosterone were lower in the COPD group and even lower in the 3A/4A COPD group. CRP and ESR levels were higher in both COPD groups, but their elevation was statistically significant only for the 3A/4A COPD group. Testosterone and free testosterone levels correlated positively with PaO2 for both COPD groups. An inverse correlation between testosterone and CRP was demonstrated for the 3A/4A COPD subgroup. Levels of testosterone correlated to FEV1, hypoxemia and weakly to CRP. The synchronous presence of the +138 insA/delA SNP resulted in even greater sex hormone level decline probably due to the presence of a more intense systemic inflammation.
Endothelin-1 (ET-1) is a potent vasoconstrictor and bronchoconstrictor but it has been shown to have also proinflammatory properties. Its ability to attract inflammatory cells in its site of production, upregulates the synthesis of adhesion molecules and stimulates the release of cytokines. The fact that cytokines have the ability to induce its synthesis and release, creates a dynamic loop for self-preservation and augmentation of the airway inflammation in Chronic Obstructive Pulmonary Disease (COPD), even after the ceasing of the noxious stimulus, i.e., cigarette smoke. Therefore, functional polymorphisms that may lead to increased levels of ET-1 may also cause an increased susceptibility to COPD development. We analyzed the longitudinal effect on lung function of two ET-1 gene polymorphisms in a population of 190 smokers (95 non-COPD and 95 COPD smokers). The two polymorphisms involved an insertion polymorphism (+138 adenine insertion 3A/4A, 138bp downstream from the transcription start site, exon 1) and a single nucleotide transversion polymorphism on exon 5 (G/T, Lys198Asn). A total of 190 subjects were enrolled in the study for each polymorphism and were followed for 3 years by annual spirometry sessions. The adjusted annual decline of forced expiratory volume in 1 second (dFEV1) was greater for those having at least one copy of the mutated gene ins/delA compared to those with the wild type allele both in the non-COPD smokers group (mean difference in dFEV, of 19.4 ml/year, p = 0.004) and COPD smokers (mean difference in dFEV1 of 11.15 ml/year, p = 0.003). On the contrary, those heterozygous for the Lys198Asn polymorphism were found to have a slower decline in FEV1 compared to those homozygous for the wild type allele. The non-COPD smokers group had a gain-in-loss of 11,24 ml/year (p < 0.001) while the COPD-smokers group had a slower decline of 11.42 ml/year (p = 0.002). Those homozygous for the polymorphisms examined show an even greater deviation from those with the wild type allele but due to the small number comprising their group, the results don't have enough statistical power. Though, they still show the trend of the effect the polymorphisms have on annual FEV1 decline. The present data shows that ET-1 and its functional polymorphisms may be implicated in COPD phenotype and severity.
Digestion is a complex process regulated by several factors. Among these, one of the most important is the time of gastric emptying. A delayed gastric emptying time can be caused by several factors and can generate considerable discomfort in humans. It ranges from mild to real debilitating disorders. Until now, different tests are suggested to study the gastric emptying time. The present review presents the mayor cause and the main symptoms linked to delayed gastric emptying and will focus on the 13C-octanoid acid breath test, as a good candidate for studying solid gastric emptying time.
Kinetic curves of the time course of the 13 CO 2 exhalation during the Kica-BT in males and females in basal condition (A) and after ethanol load (B). (% 13 C-dose/h: percentage of the dose of 13 C administered recovered in breath per hour). Times (minute) 
Cumulative dose of 13 C recovered in breath during a Kica-BT in females and males at basal condition (A) and after ethanol load (B). (% 13 C: percentage of ketoisocaproic acid oxidation). 
Kinetic curves of the time course of the 13 CO 2 exhalation during the Kica-BT in females (A) and males (B) in basal condition and after ethanol load. (% 13 C: percentage of ketoisocaproic acid oxidation). 
Cumulative dose of 13 C recovered in breath during a Kica-BT in in females (A) and males (B) in basal condition and after ethanol load. (% 13 C-dose/h: percentage of the dose of 13 C administered recovered in breath per hour and: % 13 C: percentage of ketoisocaproic acid oxidation). 
∆% cumulative dose at 60, 90 and 120 minutes before and after ethanol intake in males and females. (∆%: % 13 C difference before and after ethanol intake of ketoisocaproic acid oxidation. Min: minutes).
13C-Ketoisocaproic Acid Breath Test (13C-Kica-BT) has been proposed to assess mitochondrial function. Aim of this study is to evaluate whether gender affects mithocondrial oxidation by means of 13C-Kica-BT in healthy subjects in basal conditions and after an acute oxidative stress induced by ethanol. 50 healthy volunteers were given 1 mg/kg of 13C-Kica together with 20 mg/kg of L-leucine dissolved in 200 ml of orange juice. Breath samples were taken at baseline, every 5 minutes for 45 minutes and then every 15 minutes until 2 hours. Forty-eight hours later the test was repeated 30 min after ethanol ingestion (0.5 g/kg body weight). 13CO2 enrichment in breath was analyzed by isotope ratio/mass spectrometry. Statistical analysis was performed using the student's t test. At baseline conditions, the percentage of Ketoisocaproic acid in 2 hours was significantly higher in females than in males. Ethanol significantly reduces the oxidation of Ketoisocaproic acid. Conversely, no differences were observed between groups after the ethanol oral load. Decarboxylation of 13C-Kica was significantly higher in females than in males. Ethanol decreases Kica decarboxylation in particular in women. Further studies remain needed to establish whether sexual hormones could interfere with the metabolism of Kica.
Cumulative percentage of 13 C recovered in the breath at different time point before and after ethanol oral load using both methionines. M-met: [methyl-13 C]-methionine; L-met: L-methionine-1-13 COOH L-met at 40 and 60 p < 0.05; at 90, 105, 120 minutes , p < 0.01; M-met at 90, 105 120 minutes, p < 0.05.  
% 13 C-peak, % cum dose 60 and 120 after ethanol oral load using both methionines. M-met: [methyl-13 C]-methionine; L-met: L-methionine-1-13 COOH. * p < 0.05.
13 C-peak, % cum dose 60 and 120 in basal conditions using both methionines. M-met: [methyl-13 C]-methionine ; L-met: L-methionine-1-13 COOH. *p < 0.01.  
Percentage dose/hour of 13 C recovered in breath at different time point before and after ethanol oral load. L-met: L- methionine-1-13 COOH; M-met: [methyl-13 C]-methionine; L-met MBT: At any time p < 0.01; M-met MBT At 20, 30, 40, 60 minutes, p < 0.05.  
13C-methionine breath test has been proposed as a non-invasive tool for the assessment of human hepatic mithocondrial function. Two methionine breath labeled with 13C in differents point of his molecular structure have been used for breath test analisys. Aim of this study was to compare two differently 13C-labeled methionines in the evaluation of mitochondrial oxidation in basal conditions and after an acute oxidative stress. 15 healthy male subjects (mean age 30.5 +/- 3.1) received [methyl-13C]-methionine dissolved in water. Breath samples were taken at baseline and and 10, 20, 30, 45, 60, 75, 90, 105 and 120 minutes after the ingestion of the labeled substrate. Forthy-eight hours later, subjects underwent the same test 30 minutes after ethanol ingestion (0,3 g/kg of body weight). Seven-day later, subjects underwent breath test using (L-methionine-1-13COOH) as substrate, in basal condition and after ethanol ingestion. At basal condition, the cumulative percentage of 13CO2 recovered in breath during the test period (%cum-dose) was higher using L-methionine-1-13COOH than [methyl-13C]-methionine (10.25 +/- 1.0 vs 4.07 +/- 0.8; p < 0.01). After ethanol ingestion, % cum dose was significantly decreased at 60 and 120 minutes with both methionines (120 min: 10.25 +/- 1.0 vs 5.03% +/- 1.8; < 0.01 and 4.07 +/- 0.8 vs 2.16% +/- 0.9; p < 0.01, respectively). However, %cum-dose during L-methionine-1-13C-breath test was significantly lower than that observed during methyl-13C-methionine breath test (120 minutes: 5.03% +/- 1.8 vs 2.16% +/- 0.9; p < 0.01). In conclusion, breath test based on L-methionine-1-13COOH seems to show a greater reliability when compared to [methyl-13C]-methionine to assess mitochondrial function because a larger amount of labeled carbon that reaches the Krebs' cicle.
The evaluation of the presence and degree of liver fibrosis in patients with chronic liver disease is a fundamental diagnostic and prognostic issue. This is mainly due to the repercussions of liver fibrosis on liver function, whose derangement, in turn, is mainly responsible for the negative events of advanced liver disease. 13C-Breath Tests ((13/14)C-BTs) for the study of liver function were developed more than twenty years ago in order to non-invasively assess residual liver function in patients with various degrees of liver fibrosis, from minimal stages up to liver cirrhosis. Sequential studies that were performed over the years using various 13C-BT substrates showed that increasing degrees of liver fibrosis are paralleled by concomitant modifications in 13C-BT results. The 13C-BT probes that reportedly obtained interesting results were aminopyrine, galactose, and more recently phenylalanine. As the knowledge in this field evolved, probes for the study of specific functions, such as the 13C-Octanoate Breath Test were sought. Analysis of the published studies would seem to show that 13C-BTs alone, or in combination may provide a non-invasive picture of the functional alterations secondary to liver fibrosis. Further studies are needed to evaluate the diagnostic yield of the 13C-BT in particular clinical situations, such as in patients with normal static parameters of liver function, or after therapy.
Breath tests (BT) represent a valid and non-invasive diagnostic tool in many gastroenterological disorders. Their wide diffusion is due to the low cost, simplicity and reproducibility and their common indications include diagnosis of carbohydrate malabsorption, Helicobacter pylori infection, small bowel bacterial overgrowth, gastric emptying time and orocaecal transit time. The review deals with key points on methodology, which would influence the correct interpretation of the test and on a correct report. While a clear guideline is available for lactose and glucose breath tests, no gold standard is available for Sorbitol, Fructose or other H2 BTs. Orocaecal transit time (OCTT) defined as time between assumption of 10 g lactulose and a peak > 10 ppm over the baseline value, is a well-defined breath test. The possible value of lactulose as a diagnostic test for the diagnosis of small bowel bacterial overgrowth is still under debate. Among 13C breath test, the best and well characterized is represented by the urea breath test. Well-defined protocols are available also for other 13C tests, although a reimbursement for these tests is still not available. Critical points in breath testing include the patient preparation for test, type of substrate utilized, reading machines, time between when the test is performed and when the test is processed. Another crucial point involves clinical conclusions coming from each test. For example, even if lactulose could be utilized for diagnosing small bowel bacterial overgrowth, this indication should be only secondary to orocaecal transit time, and added into notes, as clinical guidelines are still uncertain.
Helicobacter pylori (H. pylori) is a Gram-negative bacterium able to colonize the gastric mucosa as well as gastric metaplastic areas of the duodenum, producing inflammation. The clinical outcome depends on sophisticated interactions between bacterial factors, such as the expression of determinants of virulence and pathogenicity, and host characteristics. The severity of inflammation, may then vary among different subjects, leading to the occurrence of different gastroduodenal diseases, ranging from chronic gastritis to gastric cancer and MALT-lymphoma, to some defined extragastric manifestations. Many diagnostic tests are available for the detection of H. pylori infection including noninvasive methods, such as serology, 13C-urea breath test (UBT), and fecal antigen tests and invasive techniques, including a combined use of endoscopic biopsy-based methods, such as rapid urease testing, histology, culture, and molecular methods. UBT is a highly sensitive and specific and allows to diagnose the presence or absence of infection of H. pylori, through the oral administration of a solution containing urea labelled with the non-radioactive natural carbon 13. This review article analyzes microbiological and clinical features of H. pylori as well as the different diagnostic tests able to detect this bacterium with a special focus on UBT.
LEFT PANEL: time course and 30 min cumulative exhalation of 13 CO 2 in breath after 13 C-KICA administration in healthy volunteers with normal (lean) or high body mass index (large and tall athletic individuals). In the inlet the asterisk above the black bar indicates a significant difference at 30 min between the two groups. RIGHT PANEL: cumulative recovery of 
General principles of oral 13 C-breath test for liver mitochondrial function. 1, Oral ingestion of the given 13C-substrate. 2, Duodenal jejunal absorption. 3, Liver mitochondrial metabolism. 4, Lung exhalation, measurement. 
Chemical structure, molecular formula and molecular mass of substrates used in clinical studies for the assessment of mitochondrial function. 
Breath tests employing specific 13C-labeled substrates (i.e. ketoisocaproate, methionine, octanoate) may investigate major mitochondrial pathways and their limiting steps (enzymes). Adapted from ref. 18. 
Time course of 13 CO 2 exhaled in breath after 13 C-KICA administration in healthy volunteers and in NAFLD patients. M=males (left panel), F=females (right panel). Asterisks indicate significant decrease in NAFLD patients compared to healthy controls. (Grattagliano I. and Portincasa P., unpublished observations). 
Mitochondrial dysfunction determines the onset and progression of chronic deleterious conditions including liver diseases. The in vivo assessment of mitochondrial function, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific functions and to develop diagnostic, prognostic and therapeutic strategies. The application of breath tests in the clinical setting to evaluate mitochondrial fitness may elegantly and noninvasively overcome the difficulties due to previous complex techniques and may provide clinically relevant information, i.e the effects of drugs presenting mitochondrial liabilities. Substrates meeting this requirement include alpha-ketoisocaproic acid and methionine, both decarboxylated by mitochondria. Long and medium chain fatty acids that are metabolized through the Krebs cycle and benzoic acid, which undergoes glycine conjugation, may also reflect the mitochondrial performance. This review focuses on the utility of breath tests to assess mitochondrial function in humans, thus contributing to unravel potential mechanisms associated with the dysfunction of this organelle network in the pathophysiology of liver diseases.
Breath tests are non-invasive, non-radioactive, safe, simple and effective tests able to determine significant metabolic alterations due to specific diseases or lack of specific enzymes. Carbon isotope 13C, the stable-non radioactive isotope of carbon, is the most used substrate in breath testing, in which 13C/12C ratio is measured and expressed as a delta value, a differences between readings and a fixed standard. 13C/12C ratio is measured with isotope ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer and generally there is a good agreement between these techniques in the isotope ratio estimation. 13C/12C ratio can be expressed as static measurement (like delta over baseline in urea breath test) or as dynamic measurement as percent dose recovery, but more dosages are necessary. 13C Breath-tests are involved in many fields of interest within gastroenterology, such as detection of Helicobacter pylori infection, study of gastric emptying, assessment of liver and exocrine pancreatic functions, determination of oro-caecal transit time, evaluation of absorption and to a lesser extend detection of bacterial overgrowth. The use of every single test in a clinical setting is vary depending on accuracy and substrate costs. This review is meant to present 13C the meaning of 13C/12C ratio and static and dynamic measure and, finally, the instruments dedicated to its use in gastroenterology. A brief presentation of 13C breath tests in gastroenterology is also provided.
The 13C-octanoic acid breath test is considered a useful tool to measure gastric emptying both in physiological and pathological conditions. Many studies have concerned functional dyspepsia. Recently, breath test has been used in predicting a delayed gastric emptying in subsets of dyspeptic symptoms. In detail only postprandial fullness and vomiting are resulted significantly correlated with delayed solid emptying. Besides in the patients with dyspepsia and irritable bowel syndrome associated, intestinal disturbances did not seem to contribute to delay gastric emptying. In diabetic patients octanoate test has confirmed the percentages of delayed emptying obtained by means of scintigraphy. In other organic states (celiac disease, cirrhosis, renal failure, neurological disease, etc) most of reports have proved a delayed emptying of solids. In GERD and ulcer disease gastric function is resulted normal, being accelerated in distal gastrectomy and in hyperemesis gravidarum. From pathophysiological point of view Helicobacter pylori, extrinsic autonomic neuropathy (apart from diabetes) and autoimmunity do not seem to relate with gastric emptying, both in functional and organic disease.
Sequential metabolic steps after ingestion of the 13 C-labeled baked egg yolk. The rate limiting step of 
13 CO 2 breath excretion curve (in % dose/h) and scintigraphic curve (in % gastric radioactivity retention) after administration of an egg in which the yolk has been labeled with 100 mg of 13 C-octanoic acid and the white has been doped with 2 µCi of 99m Tc-albumin colloid. Both curves are fitted by means of non linear regression analysis.
Non invasive evaluation of gastric emptying is generally performed by scintigraphy which is, however, difficult to perform and not suitable to children and childbearing women. A new method based on stable isotope breath testing analysis has been introduced in clinical practice: the 13C-octanoic acid breath test. In this paper, an overview of the current knowledge on this technique is given with special emphasis on the principle of the test, the mathematics used to analyse the results, and the physiological, pathological, and pharmacological aspects of gastric emptying studied with this new method.
13C-phenylalanine (PheBT) and 13C-galactose breath tests (GBT) explore non invasively the hepatic functional mass by measuring two enzymatic activities localized into the cytosol of liver cells: the phenylalanine hydroxylase (which converts phenylalanine into tyrosine) and the galactose kinase (which catalyzes the ATP-dependent phosphorylation of galactose to galactose 1-phosphate). Both BTs are safe and accurate in predicting the severity of liver cirrhosis showing a good correlation with the Child-Pugh score. PheBT is also used in predicting postoperative complications and monitoring liver regeneration in patients undergoing partial hepatectomy. GBT has been also used to assess liver fibrosis in patients with chronic hepatitis C. PheBT and GBT could be used in the diagnosis of two inborn errors of metabolism, phenylketonuria and galactosemia, respectively. Both BTs are not affected by enzymatic induction due to drugs which may interfere with the results of the classic "microsomial" BTs (such as the aminopyrine or caffeine BTs).
Breath tests for "dynamic" liver function evaluation have been proposed several years ago. A variety of carbon-labelled breath tests for the assessment of mitochondrial, microsomal and cytosolic liver function have been described with the aim to increase data on liver disease staging, prognosis, and response to therapy. In the last years a great interest is developed about the use of breath test for liver mitochondrial function evaluation since it results impaired in a wide range of liver diseases either of genetic or acquired origin. In these cases mitochondrial oxidative metabolism of some substrates, as far as recovery of the hepatic energy state after a metabolic insult, results impaired because of the disfunction of the electron transport chain and/or ATP synthesis. Ketoisocaproic acid and methionine are the best studied carbon-labelled substrates for the investigation of mitochondrial functional damages related to structural alterations that occur in many liver diseases. Although these tests are simple, cost-effective and safe, to date there is still not general approval for their usefulness in clinical settings since they should fulfill several requirements to overcome the drawbacks of traditional quantitative tests. On the other hand, this field is relatively young and further studies are needed in order to assess the suitable substrate for the evaluation of the complex mitochondrial metabolism both in healthy subjects and in patients with liver disease.
Conventional liver tests can be used to estimate a mixture of injury and function but none of these may be regarded as a reliable marker either to quantify functional hepatic reserve or to reflect life-threatening complications of acute and chronic liver diseases. To overcome this limit, many dynamic tests have been developed in order to evaluate the "hepatic functional mass". Among these tests we can include breath tests with 13C-labeled substrates undergoing different metabolic pathways. As concerning the evaluation of microsomal function, two main categories of breath tests have been developed based on the limiting step in the different substrates metabolism. The first group include aminopyrine, caffeine and diazepam, all substrates with a metabolism independent from hepatic blood flow and dependent almost exclusively from the enzymatic activity of different cytochromes P450. The other group is composed of substrates with flow dependent metabolism like methacetin, phenacetin, erythromycin. The aim of this review is to describe the clinical applications of microsomal liver breath tests in different hepatic diseases.
Three-dimensional, volume-rendered axial CT angiography image shows varicous dilatation of the transvers sinus, sigmoid sinus and intraserebral vascular structures with extensive intracranial abnormal vascular structures.  
Axial CT angiography image shows dural arteriovenous fistulas (DAVFs) involving right cavernous sinüs.  
Sagittal CT angiography image shows dural arteriovenous fistulas (DAVFs) involving intracranial ranging to the spinal canal.  
Dural arteriovenous fistulas (DAVF) are rare and constitute 10% to 15% of all intracranial arteriovenous malformations. Only few cases of DAVFs are reported in children. Here is the first case report describing CT angiographic findings in a 14 year old child having multiple DAVFs involving spinal canal, both cavernous and cerebral sinuses.
The objective of this study is to gain a better understanding of the antimicrobial properties of the mucus extract of snakehead fish, Channa striatus against selected human and fish pathogenic microbes. The fish mucus samples were extracted with crude, acidic and aqueous solvents to identify potential antimicrobial agents including aqueous and acid soluble compounds. The study also determined the protein content of the three different mucus extracts. The highest protein content (0.589 mg/ml) was noticed in the crude extract followed by aqueous mucus extract (0.291 mg/ml) and acidic extract (0.267 mg/ml). Preliminary screening for antimicrobial activity of all three mucus extracts were tested against 5 human pathogens (Bacillus subtilis, Klebsiella pneumoniae, Salmonella enteritidis, Proteus vulgaris and Pseudomonas aeruginosa) and fish pathogen (Aeromonas hydrophila) using the British Society for Antimicrobial Chemotherapy (BSAC) standardized disc susceptibility test method. The activity was measured in terms of zone of inhibition in mm. The acidic mucus extracts exhibited a bactericidal activity and inhibited the growth of Klebsiella pneumoniae, Pseudomonas aeruginosa and Bacillus subtilis while aqueous and crude extract showed no bactericidal activity for any of the human pathogens tested. Further test against fish pathogen Aeromonas hydrophila showed that the aqueous and crude extracts are capable of inhibiting the growth of the pathogen, demonstrating the presence of antimicrobial agents and the role of fish mucus in antimicrobial protection. The present results suggest that the mucus extracts of snakehead fish Channa striatus may be a potential source of antimicrobial agents for human and fish pathogens.
To identify key genes associated with squamous lung cancer (SLC) through analyzing gene expression data with bioinformatic tools, which could be potential biomarkers for diagnosis and treatment. Gene expression data set GSE3268 was downloaded from Gene Expression Omnibus, including 5 SLC samples and 5 healthy controls. Data pre-treatment and differential analysis were performed with packages of R. Cluster analysis was done based on gene expression values to globally present the difference between the two states. Differentially expressed genes (DEGs) were divided into up-regulated and down-regulated genes, and then underwent functional enrichment analysis with DAVID tools. WebGestalt was used to retrieve microRNAs for the DEGs and then a regulatory network was constructed. GENECODIS was selected for functional annotation for all the genes in the network. A total of 537 DEGs were obtained. Functional enrichment analysis revealed that cell cycle was significantly enriched in up-regulated genes. Besides, two microRNAs (miRNAs), MIR-142-5p and miR-9, were retrieved, which were potential tools to regulate the expression of key genes. These DEGs may be involved in pathogenesis of SLC and some of them could be potential biomarkers. Besides, MIR-142-5p and miR-9 may be utilized to treat SLC as they could modulate cell cycle.
Cow's milk (CM) allergy (CMA) is a disease of infancy, usually appearing in the first months of life. Symptoms triggered by CM at first introduction are not completely defined. The evaluation of infants for possible CMA is one of the more common problems encountered by pediatricians. Purpose of this study was to investigate the prevalence of severe reaction to CM and clinical manifestation triggered by CM administration in the nurseries. The series includes 143 prospectively studied CM-allergic babies. At the first introduction of CM, at the age of 1-8 months (median 4 months) all infants had immediate symptoms The babies were probably sensitized during the first days of life. Particularly sensitizing appears to be the exposure to CM formulas in the neonatal nursery. Little doses of allergens are more sensitizing than larger ones. We provide clear evidence of the immunological effects of oral antigen administration during the neonatal period, and discuss the possible critical allergen transmission to the nursing baby via breast milk (BM).
Robot-assisted coronary artery bypass graft (RACAB) or totally endoscopic coronary artery bypass graft (TECAB) utilizing the da Vinci surgical system is increasingly used to treat coronary heart disease (CHD), although traditional coronary artery bypass graft (CABG) remains a classic treatment. The aim of the present study was to establish the advantages and disadvantages of TECAB (or RACAB) compared with traditional CABG. PubMed and EBSCO databases were searched for studies of TECAB (or RACAB) using the da Vinci surgical system and CABG for CHD. The meta-analysis included 16 studies (2290 patients). Compared with traditional CABG, TECAB (or RACAB) had lower rates of major adverse cardiac or cerebrovascular events (MACCE) 12 months postprocedure (7.0% vs. 12.4%; odds ratio [OR], 0.53; confidence interval [CI], 0.38-0.74; p < 0.05). Subgroup analysis highlighted the differences between TECAB and RACAB as follows: TECAB decreased the rate of renal failure requiring hemofiltration (OR, 0.25; CI, 0.07-0.88), wound infection (OR, 0.11; CI, 0.11-1.99), and stroke (OR, 0.14; CI, 0.02-0.77) during follow-up, but increased the need for re-exploration for bleeding and MACCE (OR, 2.18; CI, 1.14-4.16; p < 0.05). TECAB and RACAB are safe and feasible therapies for CHD. This meta-analysis supports TECAB(or RACAB)using the da Vinci surgical system to treat CHD with reduced MACCE after 12 months. In addition, TECAB and RACAB do not increase the rates of MACCE in hospital, graft stenosis (or occlusion), and the need for reintervention compared with CABG.
Background: The aim of this study was to evaluate risk factors associated with maternal mortality in patients with eclampsia. Methods: The probable risk factors of maternal mortality including maternal age, length of hospital stay, gestational age, systolic and diastolic blood pressures; hematocrit, hemoglobin, platelet count, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase were determined from patients' charts and Odds ratios (OR) of these factors were detected using by logistic regression analysis. Results: According to logistic regression model, AST [OR, (95% Confidence Interval, CI): 7.39 (2.71-20.13)]; ALT [6.45 (2.42-17.16)]; postpartum diastolic blood pressure [4.58 (1.80-11.62)]; hematocrit [3.52 (1.86-6.65)]; hemoglobin [2.67 (2.01-3.55)] were found to be significant risk factors for maternal mortality. Conclusions: In eclamptic patients, close monitoring of particular laboratory values and blood pressure, and early intervention to alterations of certain variables will provide possibility for prevention against potential complications and subsequently decreasing mortality.
Inflammatory bowel disease (IBD) is a common disease in human resulted from a various of factors including genetic background, immune system and environment factors. Recent studies suggest pro-inflammatory cytokine IL-17 producing cell subset was involved in the disease development and the maintenance of IBD. And the differentiated and activation of IL-17 producing cells were mostly dependent on the cytokines profile secreted by innate cells in intestinal tissues. In this study, we examined the functions of IL-6 signal in regultory of IL-17 production in acute IBD model. Wildtype mice were treated with anti-IL-6 neutralizing antibodies to block IL-6 signal And then treated with DSS to induce acute IBD. Mice treated with anti-IL-6 neutralizing antibodies show severe colitis and high level of pro-inflammatory cytokine IL-17 production in DSS-induced acute IBD model when conpared with control group. Our research suggested blockade of IL-6 signal pathways in acute colitus model resulted in specifical activation of IL-17 producing cell population. Furthermore, CD44+ activated Th17 cell popualtion and CD44- IL-17 producing T cells exhibited different susceptibility to IL-6 signal in our model. Blockade of IL-6 signal in DSS-induced acuted IBD model increased IL-17 production level specifically in CD44- T cells and reduced CD44+ Th17 cell population.
Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by short lived, febrile serosae inflammatory attacks. FMF has various effects in multiple systems and organs. In the present study, our aim was to evaluate adrenal steroidogenesis in female FMF patients. There were 71 women in the study including 41 women with FMF and 30 women as healthy control group (HC group). Of 41 FMF patients, twenty were evaluated in attack period (AP-FMF group) whereas 21 of them were evaluated in attack-free period (AFP-FMF group). In all subjects; serum free testosterone, 17-OHP levels as hormones, IL-1 beta, TNF-alpha, IL-6, IL-18 as proinflammatory cytokines, CRP, fibrinogen, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) as acute phase reactants were measured in samples of venous blood taken in the morning before breakfast. Serum 17-OHP levels in AP-FMF group and AFP-FMF group were higher than in HC group (p < 0.001). A positive correlation was detected between serum levels of 17-OHP and IL-1 beta in FMF patients (p = 0.006; r = 0.486). There was no difference between FMF patients and HC group in terms of free testosterone levels (p > 0.05). Our results showed an increase in 17-OHP levels in FMF patients. These results may indicate that, regardless to the attack period adrenal steroidogenesis could be affected negatively in FMF patients.
Top-cited authors
Antonio Gasbarrini
  • Università Cattolica del Sacro Cuore
Veronica Ojetti
  • Catholic University of the Sacred Heart
Daniel de Luis
  • Universidad de Valladolid
Giuseppe Nunnari
  • Università degli Studi di Messina
Rocío Aller