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Background Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. Methods A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. Results In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p Conclusions In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. Patients often present with locally advanced disease and a staggering 50% chance of relapse following treatment. Aberrant activation of adaptive response signaling pathways, such as the cAMP/PKA pathway, induce an array of genes associated with known cancer pathways that promote tumorigenesis and drug resistance. We identified the cAMP Regulated Transcription Coactivator 2 (CRTC2) to be overexpressed and constitutively activated in HNSCCs and this confers poor prognosis. CRTCs are regulated through their subcellular localization and we show that CRTC2 is exclusively nuclear in HPV(+) HNSCC, thus constitutively active, due to non-canonical Mitogen-Activated Kinase Kinase 1 (MEKK1)-mediated activation via a MEKK1-p38 signaling axis. Loss-of-function and pharmacologic inhibition experiments decreased CRTC2/CREB transcriptional activity by reducing nuclear CRTC2 via nuclear import inhibition and/or by eviction of CRTC2 from the nucleus. This shift in localization was associated with decreased proliferation, migration, and invasion. Our results suggest that small molecules that inhibit nuclear CRTC2 and p38 activity may provide therapeutic benefit to patients with HPV(+) HNSCC.

There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS).MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment.Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing.The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness.BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

To identify the prevalence and risk factors of depression among individuals given a glaucoma-related diagnosis at a screening program.Cross-sectional community-based in a university hospital.Volunteers from a community glaucoma-screening program.After collecting sociodemographic information, participants were administered the Geriatric Depression Scale-15 (GDS-15) and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25).Participants were predominantly African American (73.5%), older than 65 years (65.7%), single (75.4%), and female (66.8%). Among 268 participants, 89 were diagnosed with glaucoma and 179 as glaucoma suspects. The frequency of depression among the glaucoma and glaucoma suspect participants was 18% and 16.2%, respectively. The mean GDS-15 score was 2.4 ± 2.7 with no difference between glaucoma and glaucoma suspect groups, p = 0.654. The mean VFQ-25 score was 78.6 ± 15.9 and was lower in glaucoma (74.7 ± 19.7) than glaucoma suspect participants (80.4 ± 13.6), p = 0.003. Risk factors for depression included difficulties with paying expenses (p = 0.017), Asian race (p0.001), and poorer scores on the VFQ-25 subscales of "General Health" (p0.001), "Distance Activities" (p = 0.024), and "Dependency" (p = 0.001).Prevalence of depression in those diagnosed with glaucoma or glaucoma suspect was higher than previous estimates of the general population. Glaucoma-screening programs might benefit from including depression-screening protocols along with referral services or low-cost treatments of depression.

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.

BACKGROUND: The purpose of this study was to examine the cost differences between preoperative and postoperative placement of gastrostomy tubes (G-tubes) in patients with head and neck cancer. METHODS: We conducted a retrospective chart review of patients with aerodigestive tract cancers from 2010 to 2015. Data included inpatient and postdischarge costs, demographics, tumor characteristics, surgical treatment, length of stay (LOS), time spent in the intensive care unit (ICU), and readmissions. RESULTS: Five hundred ninety patients were included in this study. There was a $7624 inpatient cost savings (P = .002) for those G-tubes placed preoperatively ($26 060) versus postoperatively ($33 754). Postdischarge costs did not differ significantly between groups (P = .60). There was a $9248 total costs savings (P = .009) for those patients with G-tubes placed preoperatively ($39 751) versus postoperatively ($48 999), despite patients with preoperative G-tubes having lower body mass index (BMI; P = .009), higher Association of Anesthesiologist (ASA) class (P = .02), more preoperative radiation (P < .001), and more free tissue transfer reconstruction (P = .007). CONCLUSION: There is potential for savings by placing G-tubes preoperatively, possibly driven by decreased LOS, despite data suggesting that patients with G-tubes placed preoperatively are higher risk.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion.

Background In neonatal endotracheal intubation, excessive pressure on soft tissues during laryngoscopy can determine permanent injury. Low-fidelity skill trainers do not give valid feedback about this issue. This study describes the technical realization and validation of an active neonatal intubation skill trainer providing objective feedback. Methods We studied expert health professionals’ performances in neonatal intubation, underlining chance for procedure retraining. We identified the most critical points in epiglottis and dental arches and fixed commercial force sensors on chosen points on a ©Laerdal Neonatal Intubation Trainer. Our skill trainer was set up as a grade 3 on Cormack and Lehane’s scale, i.e. a model of difficult intubation. An associated software provided real time sound feedback if pressure during laryngoscopy exceeded an established threshold. Pressure data were recorded in a database, for subsequent analysis with non-parametric statistical tests. We organized our study in two intubation sessions (5 attempts each one) for everyone of our participants, held 24 h apart. Between the two sessions, a debriefing phase took place. In addition, we gave our participants two interview, one at the beginning and one at the end of the study, to get information about our subjects and to have feedback about our design. Results We obtained statistical significant differences between consecutive attempts, with evidence of learning trends. Pressure on critical points was significantly lower during the second session (p

Human ciliopathies are hereditary conditions caused by defects of proteins expressed at the primary cilium. Among ciliopathies, Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS) and nephronophthisis (NPH) present clinical and genetic overlap, being allelic at several loci. One of the most interesting gene is TMEM67, encoding the transmembrane protein meckelin. We performed mutation analysis of TMEM67 in 341 probands, including 265 JSRD representative of all clinical subgroups and 76 MKS fetuses. We identified 33 distinct mutations, of which 20 were novel, in 8/10 (80%) JS with liver involvement (COACH phenotype) and 12/76 (16%) MKS fetuses. No mutations were found in other JSRD subtypes, confirming the strong association between TMEM67 mutations and liver involvement. Literature review of all published TMEM67 mutated cases was performed to delineate genotype-phenotype correlates. In particular, comparison of the types of mutations and their distribution along the gene in lethal versus non lethal phenotypes showed in MKS patients a significant enrichment of missense mutations falling in TMEM67 exons 8 to 15, especially when in combination with a truncating mutation. These exons encode for a region of unknown function in the extracellular domain of meckelin.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS). Subjective pain was self-evaluated by the Visual Analogue Scale (VAS). Both the tools were administered preoperatively, at 3 and 12 months' follow-up 0. The difference between the three SDS scores was significant (Friedman ANOVA, χ2 = 53.171, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative SDS scores as compared with three months follow-up (Z = -6.393, p < 0.0001) and the last, in turn, as compared with twelve months follow- up (Z = -3.720, p = 0.0002). The comparison between preoperative and 12 months' follow-up also reached significance (Z = -3.285, p = 0.001). About VAS, the difference between the three VAS scores was significant (Friedman ANOVA, χ2 = 69.932, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative VAS scores as compared with 3 months' follow-up (Z = -6.567, p < 0.0001) and the last, in turn, as compared with 12 months' follow-up (Z = -3.153, p < 0.002). The comparison between preoperative and 12 months' follow-up was also significance (Z = -5.520, p < 0.0001). Our results would alert clinicians to accurately consider the real need to treat and to include a careful psychiatric and psychological evaluation of these patients in the diagnosis and follow-up 0.

Tick borne encephalitis virus infection usually shows a biphasic course. In the first stage of illness symptoms are similar to a flu-like syndrome, then after a defervescence period, fever may represent with neurological manifestations ranging from mild meningitis to severe encephalomyelitis. We report the clinical case of an adult man presented with an acute proximal hyposthenia, severe hyperckemia, clinical and laboratoristic evidence of acute tick borne virus infection. This virus has a favourite tropism for the anterior horn cells of the cervical spine segment. Polio-like syndrome, usually affecting the upper limbs, is the clinical phenotype of an infection of the cervical motoneurons. Usually myelitis is associated to severe encephalitis and a complete diagnosis may be difficult in comatose patients. Rarely, an isolated polio-like syndrome may be the sole neurological complication of tick-borne encephalitis.

The study aim was to determine retrospectively whether the parallel use of 2 media [buffered charcoal yeast extract (BCYE) and medium of Wadowsky and Yee (MWY)] to isolate Legionella spp. from water samples taken from hospital water supply systems increased the sensitivity of the culture method as compared with methods/protocols in which only seeding on a selective medium is used. We analyzed the results obtained from 931 positive water samples. In 484 of the 931 positive water samples, Legionella spp. was isolated in the presence of other microorganisms; in 83% (400/484), we used MWY to count suspected colonies, which gave a lower number of unreadable plates. In the 447 samples containing only Legionella spp., the highest frequency of positive samples (93%, 418/447) was obtained with BCYE, whereas seeding on MWY yielded 78% (348/447) (P0.001). Evaluation of the influence of the media on the Legionella spp. counts obtained by the 2 media showed that BCYE agar produced significantly higher counts than MWY (P0.001). The major conclusions that may be drawn from our data are as follows: 1) BCYE gives a high recovery rate of positive samples (93%) and a much greater yield of Legionella spp. than MWY; 2) BCYE was necessary for the detection of non-L. pneumophila spp. which grew poorly on selective media; 3) selective media [MWY or GVPC (glycine, vancomycin, polymyxin B, and cycloheximide)] were necessary for the recovery of Legionella spp. when the non-selective medium (BCYE) was difficult to interpret because of contaminating background flora. The use of different media is recommended for routine water tests in hospitals.

Colorectal cancer (CRC) represents a major cause of morbidity and mortality. Although it is widely accepted that CRC screening in average risk populations lowers CRC incidence and mortality, a disappointedly low adherence rate to both faecal occult blood testing and colonoscopy-based screening programs has been observed in Italy and in other European countries. Main reasons for the low acceptance of colonoscopy-based CRC screening has been ascribed to lack of recommendations given by general practitioners, fear of discomfort or complications, embarrassment, and avoidance of unpleasant preparation. New advances in endoscopic technology such as colon capsule and robotic colonoscopy might represent the ideal tool for CRC screening since they reduce or eliminate procedure-related pain and discomfort. Moreover, no disinfection between procedures is required. Motion of the new probes along the gastrointestinal tract is achieved either in passive modality by utilizing the gut peristalsis (colon capsule) or in active "intelligent" modality by means of computer-assisted propulsion (robotic colonoscopy). In this review, the preliminary clinical results obtained with the new devices are summarized. It is expected that the new instruments will be soon available in clinical practice with the hope of increasing adherence to CRC screening programs.

Dobyns, William/0000-0002-7681-2844; VERLOES, Alain/0000-0003-4819-0264 WOS: 000273581000002 PubMed: 19574260 Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. US National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K23NS45832, K24HD46712, NCRR 5KL2RR025015, R01NS050375]; March of Dimes Endowment for Healthier BabiesMarch of Dimes; Ames Endowment Fund; Allan and Phyllis Treuer Endowed Chair This work was supported by the US National Institutes of Health (grants K23NS45832 to MAP, K24HD46712 to IAG, NCRR 5KL2RR025015 to DD, R01NS050375 to WBD), the March of Dimes Endowment for Healthier Babies (DD, MAP, and IAG), the Ames Endowment Fund at Seattle Children's Hospital (IAG), and the Allan and Phyllis Treuer Endowed Chair (PFC) at Seattle Children's Hospital.

Defibrotide is a polydisperse oligonucleotide with antiatherosclerotic, anti-inflammatory, anti-ischaemic, pro-fibrinolytic and antithrombotic actions without significant systemic anticoagulant effects. It has been used in the treatment of various cardiovascular disorders, and especially in endothelial complications of allogeneic stem-cell transplantation. We reviewed the published work for the mechanism of action and clinical use of defibrotide to consolidate data and to describe new applications of this drug. We reviewed the most relevant papers on defibrotide published from November 1982 to January 2008. (selected through PubMed), and used recent meeting abstracts as sources for this review. Reports have suggested that defibrotide has clinical efficacy for treatment and prophylaxis of hepatic sinusoidal obstruction syndrome occurring after stem-cell transplantation. Animal models have clearly shown the potential antineoplastic effect of this drug. Further clinical investigations are needed to clarify this new application.

Sphingosine-1-phosphate (S1P) is a pleiotropic lysolipid that has recently been implicated in the regulation of tissue fibrosis. However, the fibrogenic potential of S1P in the eye has not previously been investigated. In the current study, we evaluated cells from the anterior and posterior segments of the eye for the presence of S1P and their potential ability to produce and respond to S1P. In addition, we investigated the regulatory role of S1P as a mediator of proliferation, cellular transformation and pro-fibrotic protein expression in human retinal pigmented epithelial cells. Expression of S1P receptors and sphingosine kinases (the enzymes that produce S1P) was examined using RT-PCR, and intracellular localization of S1P was examined using immunoblotting, immunohistochemistry and ELISA in primary human retinal pigmented epithelial (RPE) cells, primary human conjunctival fibroblasts (ConF), and primary human corneal fibroblasts (CF). RPE cell proliferation was determined using an MTT-based cell proliferation assay, and RPE myofibroblast transformation, collagen type I production and profibrotic protein expression were assessed using immunofluorescence, ELISA and immunoblot. S1P(1-3, 5) receptors and sphingosine kinases 1 and 2 were expressed and intracellular pools of S1P were detected in RPE cells, ConF and CF. S1P stimulated RPE cell proliferation in a dose- and time-dependent manner. S1P induced myofibroblast transformation of RPE cells, as indicated by increased alpha-smooth muscle actin (alpha-SMA) expression and its incorporation into prominent stress fibers, and promoted collagen type I production. S1P stimulated the expression of plasminogen activator inhibitor-1 (PAI-1) and heat shock protein 47 (HSP47), two proteins that are linked to increased tissue fibrosis. Combined, these data demonstrate that RPE cells, ConF and CF from the human eye not only have the molecular ability to produce and respond to S1P, but also contain S1P. Furthermore, S1P promotes proliferation, myofibroblast transformation, collagen production and pro-fibrotic protein expression by human RPE cells. These data suggest that S1P is a previously unrecognized mediator of profibrotic cellular function and signaling in the eye.

CuZnSOD is produced in overdose in cells with trisomy 21. This has been considered to be a cause of increased oxidative stress. In the present work we have studied the catalase and glutathione peroxidase activity in fibroblasts from 6, and blood cells from 30, subjects affected by Down syndrome. In the fibroblasts, catalase and glutathione peroxidase activities did not differ significantly from control cells. In platelets, lymphocytes, polymorphs and erythrocytes, no significant increase of catalase activity was found while glutathione peroxidase activity appeared significantly increased in platelets, polymorphs and erythrocytes but not in lymphocytes. These data seem to indicate that the increase of CuZnSOD in trisomy 21 cells does not affect the production of catalase. An increase, instead, of glutathione peroxidase has been detected in all blood cells, except in lymphocytes; this is a sign of a greater need for protection against the risk of lipoperoxidation. The fact that the enhancement of glutathione peroxidase activity could be assessed only in some types of cells examined suggests that the observed increase in those cells is probably a result of an additive effect of the overproduction of CuZnSOD due to gene dosage and the ordinarily higher content of oxygen radicals and peroxides.

Respiratory problems are among the main causes of mortality for preterm newborns with pulmonary diseases; mechanical ventilation provides standard care, but long-term complications are still largely reported. In this framework, continuous medical education is mandatory to correctly manage assistance devices. However, commercially available neonatal respiratory simulators are rarely suitable for representing anatomical and physiological conditions; a step toward high-fidelity simulation, therefore, is essential for nurses and neonatologists to acquire the practice needed without any risk. An innovative multi-compartmental infant respirator simulator based on a five-lobe model was developed to reproduce different physio-pathological conditions in infants and to simulate many different kinds of clinical scenarios. The work consisted of three phases: (1) a theoretical study and modeling phase, (2) a prototyping phase, and (3) testing of the simulation software during training courses. The neonatal pulmonary simulator produced allows the replication and evaluation of different mechanical ventilation modalities in infants suffering from many different kinds of respiratory physio-pathological conditions. In particular, the system provides variable compliances for each lobe in an independent manner and different resistance levels for the airway branches; moreover, it allows the trainer to simulate both autonomous and mechanically assisted respiratory cycles in newborns. The developed and tested simulator is a significant contribution to the field of medical simulation in neonatology, as it makes it possible to choose the best ventilation strategy and to perform fully aware management of ventilation parameters.

Background Mechanical ventilation is a therapeutic action for newborns with respiratory diseases but may have side effects. Correct equipment knowledge and training may limit human errors. We aimed to test different neonatal mechanical ventilators’ performances by an acquisition module (a commercial pressure sensor plus an isolated chamber and a dedicated software). Methods The differences (ΔP) between peak pressure values and end-expiration pressure were investigated for each ventilator. We focused on discrepancies among measured and imposed pressure data. A statistical analysis was performed. Results We investigated the measured/imposed ΔP relation. The ΔP do not reveal univocal trends related to ventilation setting parameters and the data distributions were non-Gaussian. Conclusions Measured ΔP represent a significant parameter in newborns’ ventilation, due to the typical small volumes. The investigated ventilators showed different tendencies. Therefore, a deep specific knowledge of the intensive care devices is mandatory for caregivers to correctly exploit their operating principles.

Primary objective: To describe the outcome of near-drowning and rehabilitation contexts for recovery.Methods and procedures: Standardized measures were used to emphasize the functional impact of deficits over the first year post-injury in three children

In performing the sit-to-stand transition, young children (6- to 7-year-olds) were expected to display a movement form similar to that of adults. However, movement consistency was predicted to be poorer in children than in adults because they lack refinement of motor control processes. Kinematic analysis of 10 repetitions of the sit-to-stand movement was carried out for 6 typically developing children and 6 adults. Supporting the authors' prediction of comparable form, no differences were evident between age groups for sequence of joint onsets, proportional duration of segmental motion, or in angle-angle plots of displacement at 2 segments. In contrast, within-participant variability was found to be higher for children: Coefficients of variation for most kinematic measures were twice those seen for adults. The authors interpret the children's lack of movement consistency as a reflection of inadequate stabilization of an internal model of intersegmental dynamics. Whereas adults have attained a skill level associated with refinement of that model, children have not. Children have an additional control problem because changes in body morphology throughout childhood require ongoing updating of the internal model that controls intrinsic dynamics.

Pulmonary alveolar microlithiasis (PAM) (MIM 265100) is a rare, autosomal recessive pneumopathy characterized by intra-alveolar formation and accumulation of tiny, roundish corpuscles called “microliths”. The name “alveolar microlithiasis” was first used by Puhr in 1933; since then, several reports have appeared, and over 300 individuals with this condition have been reported. We have reviewed the PAM cases in the literature in light of personal experience, focusing on medical implications, disease diagnosis and progression over time, familial predisposition, and geographical and sex distribution. This study confirms autosomal recessive inheritance and does not support the role of other, non-genetic, factors in the pathogenesis of PAM. © 2002 Wiley-Liss, Inc.

CCNU and methotrexate were employed as salvage treatment in 34 small cell lung cancer patients resistant to CAV/PE alternating Induction chemotherapy. In the 33 evaluable patients we observed an objective response rate of 21.2 % and 3 % complete response; median survival was 4 months with 2 patients alive 18 months from starting salvage chemotherapy. The treatment was well tolerated. CCNU and methotrexate has shown to be a moderately active and tolerable salvage treatment for small cell lung cancer after CAV/PE alternating first-line chemotherapy.

OBJECTIVE: Hypoglycemia is common in type 1 diabetes mellitus (T1DM). We aimed to update the incidence of severe and symptomatic hypoglycemia and investigate several correlated factors. METHODS: In this multicenter, observational retrospective study, the data of 206 T1DM patients from a sample of 2,229 consecutive patients seen at 18 diabetes clinics were analyzed. Sociodemographic and clinical characteristics, severe hypoglycemia in the past 12 months, and symptomatic hypoglycemia in the past 4 weeks were recorded with a self-report questionnaire and a clinical form during a routine visit. Poisson multivariate models were applied. RESULTS: A minority of patients accounted for the majority of both severe and symptomatic episodes. The incidence rate (IR) of severe hypoglycemia was 0.49 (0.40-0.60) events/person-years. The incidence rate ratio (IRR) was higher in patients with previous severe hypoglycemia (3.71; 2.28-6.04), neuropathy (4.16; 2.14-8.05), long duration (>20 years, 2.96; 1.60-5.45), and on polypharmacy (1.24; 1.13-1.36), but it was lower when a complication was present. The IR of symptomatic hypoglycemia was 53.3 events/person-years, with an IRR significantly higher among women or patients with better education, or shorter duration or on pumps. The IRR was lower in patients with higher BMI or neuropathy or aged more than 50 years. CONCLUSIONS: Fewer than 20 % of T1DM patients are free from hypoglycemia, with one in six having experienced at least one severe episode in the last year. The distribution is uneven, with a tendency of episodes to cluster in some patients. Severe and symptomatic episodes have different correlates and reflect different conditions.

This prospective study was done to evaluate the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano from a short follow up period (one year).This randomized clinical trial of 26 patients was performed during the period from January 2012 to July 2012. Nineteen men and seven women were treated for a fistula-in-ano with a commercial fibrin glue injection. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified and the fistula tract was accurately curetted. Fibrin glue was introduced by a loaded double-channel syringe into the external fistula opening until the fibrin glue tip could be seen emerging from the internal opening.The initial success rate was 76.9% (20/26). Recurrence rate was 23% (6/26). Four patients underwent a re-application of fibrin glue and the fistulas of these patients closed. Total recurrence rate was 7.6% (2/26). The overall success rate was 69.2% (18/26).Fibrin glue application was thus found to be an easy, safe, successful alternative treatment in the management of fistulas-in-ano. Specifically, this therapeutic option demonstrated his efficacy for simple non-ramificated transsphincteric and intersphincteric fistulas. Multicentric randomized clinical trials with more representative sample seem to be necessary to investigate the best patients to treat by fibrin glue injection and the optimal application technique to improve these results.

Borderline ovarian tumors (BOTs) represent a type of epithelial tumors having a biologic intermediate behavior between clearly malignant and straight benign tumors. Most of BOTs interest women during fertile age, for which it is necessary to consider a fertility sparing surgery.To evaluate the clinical aspects and pregnancy rate of women affected by borderline ovarian tumors who have undergone fertility sparing surgery.A study of 22 patients affected by BOTs who have been treated with a fertility sparing surgery was conducted between January 2005 and October 2011 at Sant'Andrea Hospital, "Sapienza" University of Rome. The patients' characteristics analyzed were: age, histological type, tumor size, adnexal surgery, pre-operative serum CA-125, diagnostic circumstances, number of patients who became pregnant and number of overall pregnancies.Among the 22 patients treated with a fertility sparing surgery, only sixteen wanted to get pregnant. Eleven patents out of 16 accomplished it. The pregnancy rate was 68.7%.Fertility sparing surgery can be considered a safe procedure for young women affected by borderline ovarian tumors.

Parasite infections have long been associated with specific types of human cancers. Schistosoma hematobium is an inducer of urinary bladder cancer, Helicobacter pylori is a gastric carcinogen, and hepatitis B virus and Opisthorchis viverrini are causative agents of hepatocellular carcinoma. Another liver fluke, Fasciola hepatica, has also been identified as a neoplastic risk agent, primarily in animals. We used F. hepatica-induced inflammation in mice to determine if the presence of an aggressive liver fluke could induce mutagenic events in mammalian tissue. This provides a perspective on the relationship between chronic inflammation and cancer and may be a model for future studies on this complex association. In previous studies using the Big Blue® transgenic mouse assay, we demonstrated an increase in lacI mutations in liver cells harvested from mice harboring F. hepatica flukes when compared to uninfected control animals. In these studies, we report on the types of mutations associated with this parasite infection. The observed mutational spectrum roughly corresponded to the spectrum of spontaneous mutations in liver cells when compared to control (uninfected) animals. However, the spectrum of mutations from parasitized animals showed a significant increase in complex changes and multiple mutations (18.2%) when compared to what would be expected from control animals (2.8%).

Several studies have investigated the frequency of epileptic seizures following ischemic strokes and transient ischemic attacks (TIAs). Little attention has been paid to the possibility that seizures may be precipitated by TIAs. We examined if seizures can be the only symptom of a TIA and how often this might occur. We performed a retrospective analysis of clinical charts and electroencephalograms of 160 consecutive patients evaluated for a first-ever seizure from January 1997 to December 1999 at Belluno General Hospital. From January to May 2000, 19 more first-ever seizure patients were evaluated directly. Four patients (2%) had seizures in the presence of important risk factors for ischemic stroke (atrial fibrillation in two patients, atrial fibrillation and ventricular mural thrombus in one patient, hemodynamically significant left carotid stenosis in one patient). Seizures were not accompanied by other neurological deficits or brain lesions on CT or MRI. As risk factors for brain ischemia are frequent in the general population not developing seizures, our results do not prove that the occurrence of seizures was more than casual in these patients. Yet they indicate that in a small percentage of patients, seizures can occur in a context highly suggestive of TIA, with no other focal deficits.

We report a case of ocular surface neoplasia in a patient with history of radial keratotomy and laser in situ keratomileusis. In vivo confocal microscopy of the cornea was useful to evaluate whether the incisions and scars of previous refractive surgeries were involved and to establish appropriate therapy.

Objectives – Few case-control studies of first-ever transient global amnesia (TGA), transient ischemic attack (TIA) and normal controls have been performed to date. We aimed to assess the prevalence of cerebrovascular risk factors in a well defined population of TGA patients. Material and methods – We undertook a retrospective and prospective community-based case-control study of 170 first-ever TGA, 170 first-ever TIA and 170 normal controls. Results – Age-matched analysis revealed that TGA cases had a significantly lower prevalence of atrial fibrillation and diabetes mellitus than TIA controls. The prevalence of cigarette smoking and diabetes mellitus was significantly higher in normal controls than in TGA cases. Conclusion – Our community-based case-control study showed that atrial fibrillation and diabetes mellitus, two important risk factors for cerebrovascular disease, were significantly more common in the TIA group than in the TGA one. These results make the thromboembolic pathogenesis of TGA unlikely.

Mechanical ventilation is a current support therapy for newborns affected by respiratory diseases. However, several side effects have been observed after treatment, making it mandatory for physicians to determine more suitable approaches. High fidelity simulation is an efficient educational technique that recreates clinical experience. The aim of the present study is the design of an innovative and versatile neonatal respiratory simulator which could be useful in training courses for physicians and nurses as for mechanical ventilation. A single chamber prototype, reproducing a pulmonary lobe both in size and function, was designed and assembled. Volume and pressure within the chamber can be tuned by the operator through the device control system, in order to simulate both spontaneous and assisted breathing. An innovative software-based simulator for training neonatologists and nurses within the continuing medical education program on respiratory disease management was validated. Following the clinical needs, three friendly graphic user interfaces were implemented for simulating three different clinical scenarios (spontaneous breathing, controlled breathing and triggered/assisted ventilation modalities) thus providing physicians with an active experience. The proposed pulmonary simulator has the potential to be included in the range of computer-driven technologies used in medical training, adding novel functions and improving simulation results.

Background and Purpose We sought to register the incidence rate, risk factors, and case-fatality rate of all the new cases of first-ever-in-a-lifetime stroke in the province of Belluno, Italy. This study aimed to provide an epidemiological survey of cerebrovascular disease that could supply investigative objectives and support information for regional healthcare facilities planning. Methods We undertook a prospective population-based study in the territory of the 1st, 2nd, 3rd, and 4th local health units in the province of Belluno, an area located in northeast Italy (population, 211 389). Results In the first year of the study (June 1, 1992, to May 31, 1993), 474 cases of first-ever stroke were registered. The crude annual incidence rate was 2.24/1000 (2.01/1000 for men and 2.45/1000 for women). After adjustment to the European population, the incidence rate for first stroke was 1.70/1000 per year. The pathological diagnosis was confirmed by a CT scan in 89.5% of cases. Cerebral infarction accounted for 319 cases, while 93 patients suffered a primary intracerebral hemorrhage, 12 patients a subarachnoid hemorrhage, and 50 patients a stroke of unknown origin. The overall 30-day case-fatality rate was 33%, and the mortality within the first week from stroke onset was 23%. The recurrence rate after 1 month was 1.9%. After 1 month, 46% of our patients were functionally independent in activities of daily living. Conclusions Our first-year results confirm the fairly high risk for stroke in central and northern Italy and support European findings regarding risk factors for stroke.

To evaluate the feasibility of examining aberrant right subclavian artery (ARSA) at first and second trimester gestation, its prevalence and associations in an unselected population.Right subclavian artery (RSA) was prospectively evaluated in 6617 routine patients. When ARSA was detected, fetal echocardiography was offered and fetal karyotyping was discussed. If invasive testing was performed with normal karyotype, fluorescence in situ hybridization for 22q11.2 microdeletion and additionally, in case of nuchal translucency (NT) measurement above the 99(th) centile, oligo array-based comparative genomic hybridization, were offered. In all aneuploidies, NT and first trimester additional ultrasonographic (US) markers assessment (nasal bone, tricuspid valve, ductus venosus) were recorded.RSA assessment was feasible in 85.3% and 98% of first and second trimester examinations, respectively (overall feasibility 94%). There were detected 89 ARSA (1.42% of the feasible cases), of which 66 in the first trimester. More than 20% were associated to other abnormalities: 10 aneuploidies; 2 microdeletions (15q11.2 and 22q11.2); in the euploid fetuses, 8 associated abnormalities were observed, 4 of which were cardiac defects. In the case of 22q11.2 microdeletion, ARSA was associated only with increased NT.Prenatal routine US assessment of the RSA is feasible by highly experienced operators in first trimester screening. There is an important association of ARSA detected in unselected population with fetal abnormalities, including aneuploidies, cardiac defects and genetic anomalies. In trisomy 21 fetuses, ARSA can be the only first trimester US marker or, when associated to increased NT, it can represent the only 'additional' marker.

Milligan-Morgan operation is still considered the treatment of choice for IV-degree haemorrhoids: it is frequently associated with significant postoperative pain and prolonged hospital stay. Many instruments were conceived to reduce these complications, such as the LigaSure™ (LS) system, a combination of radiofrequency and pressure that seems mainly effective where a large tissue demolition is required. This randomized study isFifty-two patients with IV-degree hemorrhoids were randomly assigned to two different surgical treatments (conventional diathermy vs. LigaSure™ hemorrhoidectomy). They were evaluated on the basis of the following main outcomes: mean operative time, postoperative pain, day of discharge early and late complications. The time of recovery of work was also assessed. All patients had a minimum follow-up of twelve months (range 12-24). All data were statistically evaluated.Twenty-seven patients were treated by conventional diathermy, 25 by LigaSure™. The mean operative time was significantly shorter in LS, such as postoperative pain, mainly lower on the third and fourth postoperative day: moreover pain disappeared earlier in LS than CD. The time off-work was shorter in LS, while there was no difference in hospital stay and overall complications rate .This randomized prospective controlled trial confirms, according to other large trials in literature , the benefits of the LigaSure™ hemorrhoidectomy over conventional diathermy when a large tissue demolition is required, supporting the use of this device as treatment of choice in IV degree hemorrhoids, even if the procedure is more expensive than conventional operation.

in the technology associated with the detection and assessment of environmental carcinogens and mutagens should be accompanied by progress in the planning and optimal deployment of these techniques, especially in developing countries. At present, we are moving toward a situation where advanced techniques are used in a seemingly random and probably suboptimal way. The six areas considered worthy of international and national coordination are discussed below.

Leishmaniasis is a zoonosis caused by a protozoan of the Leishmania genus. First-line treatment for all forms is currently represented by the use of antimony derivatives, although toxic effects and the number of resistant strains in both immunocompromised and immunocompetent patients is increasing. Liposomal amphotericin B (L-AMB) is less toxic, more effective, and better tolerated, especially in human immunodeficiency virus-negative immunocompromised patients. We present 2 cases of transplanted patients affected by visceral leishmaniasis treated successfully with L-AMB.

We examined intensive walking practice using two instructional strategies on gait in Parkinson’s disease (PD) before and after training and on delayed retention tests. During four training sessions (15 practice trials of walking per session), subjects (N = 6 per group) were given either verbal instruction (VI) to “take a big step” or VI plus augmented feedback (FB). For FB, videotape performance-feedback (from prior trial) supplemented by performance-cues (for subsequent trial) was given after each trial. On pre- and posttests (1 week after training), the only instructions were to “walk as well as you can.” For available subjects (N = 7), retention was tested at 3, 6, or 12 months after training. Gait parameters were derived from kinematic analysis of walking during training and testing. From pre- to posttests, stride length, walking velocity and shoulder excursion increased significantly, with no change in cadence. Improvements in stride length and gait velocity above pretest levels were maintained on retention tests. During training and testing, no effects of VI versus VI + FB were found. Although the two instructional strategies did not differ, intensive practice walking with VI improved the gait pattern of individuals with PD and these gait improvements were maintained over an extended period of time.

Background The prevention and control of legionellosis in hospital settings involves environmental sampling, among other measures. The data yielded by sampling constitute an important means of risk assessment and provide a valid basis on which to plan remedial (cleansing and disinfection) and preventive (maintenance) interventions. This retrospective study had 2 objectives: (1) to evaluate the utility of biofilm sampling at distal sites and (2) to identify an efficient environmental sampling strategy. Methods Samples of hot water and biofilm were collected between June 1999 and March 2008 from 41 hospitals in Italy's Piemonte region. We analyzed results of the samples (water and biofilm) taken from the same site and results of the water samples taken from the recirculation loop and water samples taken from the distal sites during the same sampling run. Results Microbiological analysis was performed on 3910 pairs of samples (water/biofilm). In 81% of the pairs, the results were concordant; in 17% of the pairs, Legionella was isolated only from the water samples, and in only 2% of the pairs was Legionella isolated from the biofilm sample alone. Data from 299 sampling runs show that 79% (236) of results from the water samples taken from the recirculation loop and water samples taken from the distal sites during the same sampling run were concordant, and 21% (63) were discordant. Conclusions Our findings suggest that hospitals could safely adopt a simpler (water sampling only without biofilm sampling) and more efficient (monitoring of the entire system through sampling of recirculation loop water) environmental sampling policy.

Background and Purpose . Task-related training (TRT) but not resistive exercise (RE) was found to improve the path of the hand of a hemiparetic upper extremity when reaching to targets. Forward movement of the trunk, however, compensated for the poststroke motor impairment. Prior studies also demonstrated that short-term practice of reaching to grasp objects with truncal motion restrained (compared to unrestrained practice) increased elbow extension, lessened compensatory trunk movement, and improved interjoint coordination during performance with the trunk unrestrained. Objective. To determine the effects of TRT and RE on unrestrained reaching following extended practice in which compensatory truncal motion was limited. Methods. Using a restraining device to reduce movement of the trunk, hemiparetic patients with moderately severe motor impairment were given 12 sessions over 4 weeks of TRT (n = 5) or RE (n = 6). Reaching when the trunk was not restrained to targets located ipsilateral, midline, and contralateral to the impaired arm was tested before and 2 days after training by 3D kinematic analyses. Results. After both training protocols, kinematic analysis showed that trunk flexion decreased ( P < .01, η2 = .53) scapular motion shifted toward protraction ( P < .01, η2 = .57) and elbow extension increased ( P < .04, η2 = .39). Only after TRT did the path of the hand straighten ( P < .02, η2 = .46), deceleration time decrease ( P < .03, η2 = .44), and, at the difficult ipsilateral target, shoulder flexion increase ( P < .03, η 2 = .31). Conclusions. Training that restricted compensatory truncal motion during TRT improved the precision of reaching more than during RE. Truncal restraint during rehabilitation of reaching may be an effective therapeutic strategy in patients with moderately severe hemiparetic stroke, especially when combined with TRT.

The purpose of the present study was to determine possible cross-reactivity between different serogroups or between different species by means of bacterial smears of individual L. pneumophila serogroups and several non-pneumophila Legionella spp. Using BIOCHIP slide we found a considerable frequency of cross-reactions with L. pneumophila serogroup 12 (88.4%) therefore BIOCHIP slide proved as useful method for identification of cross-reactivity between members of the Legionnellaceae.

Joubert syndrome-related disorders (JSRDs) are autosomal recessive pleiotropic conditions sharing a peculiar cerebellar and brainstem malformation known as the 'molar tooth sign' (MTS). Recently, mutations in a novel ciliary gene, RPGRIP1L, have been shown to cause both JSRDs and Meckel-Gruber syndrome. We searched for RPGRIP1L mutations in 120 patients with proven MTS and phenotypes representative of all JSRD clinical subgroups. Two homozygous mutations, the previously reported p.T615P in exon 15 and the novel c.2268_2269delA in exon 16, were detected in 2 of 16 families with cerebello-renal presentation ( approximately 12%). Conversely, no pathogenic changes were found in patients with other JSRD phenotypes, suggesting that RPGRIP1L mutations are largely confined to the cerebello-renal subgroup, while they overall represent a rare cause of JSRD (

Metastatic disease is the most frequent intraocular malignancy in adults. The most common sites of origin are breast and lung. The vast majority of metastatic intraocular tumours are carcinomas, and rarely neuroendocrine tumours and sarcomas. Gastrointestinal stromal tumours (GIST) constitute a distinct group of gastrointestinal tumours arising from the interstitial cells of Cajal, regulators of peristalsis. The development of imatinib mesylate, a receptor tyrosine kinase inhibitor, has made a major impact on the management of advanced GISTs. We report the case of a patient with choroidal and systemic disease from a GIST, who underwent therapy with imatinib. An accurate diagnosis is required since therapy may differ from the most common metastatic carcinomas. A …

Classic galactosaemia is a potentially lethal inborn error of metabolism that results from profound impairment of galactose-1P uridylyltransferase (GALT). Like many autosomal recessive disorders, classic galactosaemia demonstrates marked allelic heterogeneity; many if not most patients are compound heterozygotes. Owing in part to the fact that most GALT mutations are never observed in patients in the homozygous state, in part to concerns of possible allelic interaction, and in part to the broad range of GALT activity levels associated with the affected, carrier, and control states, definition of the specific functional consequence of individual variant GALT alleles from studies of clinical samples alone can be a challenging task. To overcome this problem we previously developed and applied a null-background yeast system to enable functional analyses of human GALT alleles expressed individually or in defined pairs. We report here the application of this system to characterize three distinct variant alleles of GALT identified within a single family. Of these alleles, one carried a missense mutation (K285N) that has previously been reported and characterized, one carried a nonsense mutation (R204X) that has previously been reported but not characterized, and the third carried a missense substitution (T268N) that was novel. Our studies reported here reconfirm the profound nature of the K285N mutation, demonstrate that the R204X mutation severely compromises both expression and function of human GALT, and finally implicate T268N as one of a very small number of naturally occurring rare but neutral missense polymorphisms in human GALT.

Summary Background Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder, three types of which have been described in the literature. All of them are characterized by alopecia, facial dysmorphism and bone deformities. Deletions and nonsense mutations of the TRPS1 gene are responsible for most of the TRPS I and III cases with no clear genotype–phenotype correlation. The majority of missense mutations have been described at TRPS1 exon 6, encoding a presumptive GATA DNA-binding domain, and are known to be associated with the most severe forms of the phenotypic spectrum of TRPS. Mutation mapping at exon 7 described to date includes nonsense mutations and a familial case with an insertion mutation. Objectives To determine a possible correlation between a mutation at exon 7 and mild TRPS phenotype. Methods We describe three members of an Italian family with TRPS I. All three showed clinical features typical of TRPS I such as temporal alopecia and facial abnormalities, but no mental retardation. Results Mutation analysis showed a missense mutation (R952C) in exon 7 of the TRPS1 gene. Conclusions R952C is the first missense mutation described outside the GATA zinc-finger domain of TRPS1. In contrast with missense mutations occurring within this region, this mutation prevents the transport of the TRPS1 protein into the nucleus, therefore determining TRPS I by haploinsufficiency. We hypothesize that a TRPS exon 7 mutation could result in a mild phenotype.

The reaction times and kinematics of reach and grasp were analyzed for eight subjects with Parkinson's disease (PD) and eight healthy subjects during three variations of a maximal speed prehension task: (a) grasping a stationary ball as fast as possible, (b) grasping a stationary ball within specific time constraints (520 ms and 450 ms), and (c) grasping a moving ball within the same time constraints. Subjects with PD exhibited bradykinesia when reaching for a stationary ball. When reaching for a moving or stationary ball with temporal constraints, subjects with PD moved as fast as healthy subjects. The reaction times of both groups were shorter when reaching to a moving ball than to a stationary ball, regardless of the time constraint. Subjects with PD had a slower velocity of hand opening and closing, a smaller maximal aperture, and a longer time to maximal aperture than healthy subjects in all task conditions. Thus, visual motion cues and external temporal constraints had a greater effect on reach than on grasp. The results suggest that the bradykinesia observed in individuals with PD during self-determined maximal speed prehension may reflect a strategy used to compensate for deficiencies in the grasp component of the task.

Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux.To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter.Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year.In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls.Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.