New multiplex real-time PCR approach to detect gene mutations for spinal muscular atrophy

Abstract

Background

Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation.

Methods

The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR.

Results

The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA.

Conclusion

The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

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Corynebacterium cutis Lysate Treatment Can Increase the Efficacies of PPR Vaccine

Journal of Interferon & Cytokine Research , Vol. 0, No. 0.


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Doctor, PAP thyself: commentary on Yasmin R, Muntham D, and Chirakalwasan N’s Uncovering the sleep disorders among young doctors

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Uncovering the sleep disorders among young doctors

Abstract

Purpose

Sleepiness and tiredness are common complaints among young doctors. Sleep deprivation is believed to be the main culprit. However, we believe that there may be other sleep disorders which may contribute to these symptoms such as occult obstructive sleep apnea (OSA).

Methods

A prospective cross-sectional study was performed among young doctors less than 40 years old, working at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, and Hospital Kuala Lumpur, Kuala Lumpur, Malaysia, using questionnaires and home sleep apnea testing (Apnealink™Plus). The primary objective of this study was to evaluate the prevalence of OSA (apnea-hypopnea index (AHI) ≥5). The secondary objectives were to evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) defined by AHI ≥5 + excessive daytime sleepiness (EDS), sleep deprivation (the difference of weekend (non-workdays) and weekday (workdays) wake-up time of at least 2 h), EDS (Epworth Sleepiness Scale score ≥10), tiredness, and perception of inadequate sleep as well as to identify their predictors.

Results

Total of 52 subjects completed the study. Mean age and mean body mass index (BMI) were 31.3 ± 4 and 23.3 ± 3.6, respectively. The prevalence of OSA and OSAS were 40.4 and 5.8 %, respectively. One third of OSA subjects were at least moderate OSA. Prevalence of sleep deprivation, EDS, tiredness, and perception of inadequate sleep were 44.2, 15.4, 65.4, and 61.5 %, respectively. History of snoring, being male, and perception of inadequate sleep were significant predictors for OSA with the odds ratio of 34.5 (p = 0.016, 95 % CI = 1.92–619.15), 18.8 (p = 0.001, 95 % CI = 3.10–113.41), and 7.4 (p = 0.037, 95 % CI = 1.13–48.30), respectively. Only observed apnea was a significant predictor for OSAS with odds ratio of 30.7 (p = 0.012, 95 % CI = 2.12–442.6). Number of naps per week was a significant predictor for EDS with the odds ratio of 1.78 (p = 0.007, 95 % CI = 1.17–2.71). OSA and total number of call days per month were significant predictors for tiredness with the odds ratio of 4.8 (p = 0.036, 95 % CI = 1.11–20.72) and 1.3 (p = 0.050, 95 % CI = 1.0004–1.61), respectively. OSA was the only significant predictor for perception of inadequate sleep with the odd ratios of 4.5 (p = 0.022, 95 % CI = 1.24–16.59).

Conclusions

Our results demonstrated relatively high prevalence of OSA and OSAS among young doctors. Snoring, being male, and perception of inadequate sleep were significant predictors for OSA. Observed apnea was a significant predictor for OSAS. OSA was a significant predictor for tiredness and perception of inadequate sleep.

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Could tea polyphenols be beneficial for preventing the precocious puberty?

Publication date: Available online 16 August 2016
Source:Medical Hypotheses
Author(s): Youmei Wu, Jialu Wang, Wei Cai, Xiuhua Shen
Precocious puberty which impacts children physically and psychologically has become one of the health problem over the world. However, the mechanism and preventive measures of precocious puberty is still not clear. Recent studies suggested that leptin may act as the 'permissive factor' to initiate the puberty by regulating gonadotrophin-releasing hormone secretion. Previous evidence from animal and human studies found that tea polyphenols can reduce serum leptin levels in vivo and inhibit the expression of leptin in adipose tissue. This article focus on whether tea polyphenols could delay the onset of puberty by reducing leptin levels. To verify the possibility of tea polyphenols on preventing precocious puberty, animal experiment can be used. Our hypothesis that tea polyphenols could prevent the precocious puberty may provide important potential way for the prevention and control of children precocious puberty.



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Location of a biliary leak after liver resection determines success of endoscopic treatment

Abstract

Background

Bile leaks after hepatic resection are serious complications associated with substantial morbidity and mortality. The aim of this prospective observational study was to determine the therapeutic success of endoscopic treatment of biliary leakage after liver resection.

Patients and methods

Grade B biliary leaks were considered for endoscopic treatment in patients after liver resection between 1/09 and 4/12. Endoscopic treatment (sphincterotomy only, plastic stent distal to leak or bridging) was defined as successful when the patient remained without symptoms after drain removal and without extravasation follow-up ERC 8 weeks later.

Results

Overall rate of biliary leak was 7.4 % (61/826). 35 patients with a grade B bile leak were considered for endoscopic treatment. 22 (63 %) had bile leaks that were peripherally located, and 13 (37 %) had bile leaks at central location. In 3 patients, sphincterotomy only was performed; in 19 patients, a stent distal to the leak and in 13 patients, a bridging stent was inserted. The overall success rate was 74 % (26/35 patients). Endoscopic treatment failed in 26 % (9/35), and mortality rate was 11 % (4/35). In all patients with leaks located at the right or left hepatic duct, treatment with the bridging stent was successful.

Conclusion

Endoscopic therapy for biliary leakage after liver resection is safe and effective and should be considered as a first-line therapy in patients who are suitable for an interventional, non-surgical approach. Patients with a centrally located leak who are treated with a bridging stent are more likely to benefit from endoscopic intervention.

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Modulation of Upper Esophageal Sphincter (UES) Relaxation and Opening During Volume Swallowing

Abstract

UES opening occurs following cricopharyngeus deactivation and submental muscle contraction causing hyolaryngeal elevation and UES distraction. During impedance manometry, the inverse of impedance (admittance) can be used to measure bolus presence and infer UES opening. We hypothesized that the temporal relationship between UES relaxation, opening and hyolaryngeal elevation would change with increasing bolus volume. Simultaneous intramuscular cricopharyngeal (CP) electromyography (EMG), surface submental EMG (SM-EMG), and high-resolution impedance manometry were recorded in eight (aged 27 ± 7 years, 5 M) healthy volunteers, while swallowing 0.9 % saline boluses of 2, 5, 10, and 20 ml. Data were exported and analyzed via Matlab. Statistical analysis comprised repeated measures one-way ANOVA and Pearson correlation. A P value of <0.05 was considered significant. Duration of CP deactivation increased at 20 ml volume (P < 0.001). UES relaxation and opening increased with increasing bolus volume (P < 0.001); however, overall duration of SM activation did not change. As UES opening occurs progressively earlier with increasing volumes, peak SM-EMG activity occurs relatively later (P < 0.001) and shifts from occurring before to following peak UES distention. During healthy swallowing, there is sensory modulation of cricopharyngeal and submental muscle activity. Intrabolus pressures, transmitted from the tongue base and pharynx, play a progressively more important role in sphincter opening with increasing volume. The findings may explain why some healthy elderly and patients with oropharyngeal dysphagia have difficulty swallowing larger while tolerating smaller bolus volumes.

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Characterisation of myocardial structure and function in adult-onset growth hormone deficiency using cardiac magnetic resonance

Abstract

Growth hormone (GH) can profoundly influence cardiac function. While GH excess causes well-defined cardiac pathology, fewer data are available regarding the more subtle cardiac changes seen in GH deficiency (GHD). This preliminary study uses cardiac magnetic resonance imaging (CMR) to assess myocardial structure and function in GHD. Ten adult-onset GHD patients underwent CMR, before and after 6 and 12 months of GH replacement. They were compared to 10 age-matched healthy controls and sex-matched healthy controls. Left ventricular (LV) mass index (LVMi) increased with 1 year of GH replacement (53.8 vs. 57.0 vs. 57.3 g/m², analysis of variance p = 0.0229). Compared to controls, patients showed a trend towards reduced LVMi at baseline (51.4 vs. 60.0 g/m², p = 0.0615); this difference was lost by 1 year of GH treatment (57.3 vs. 59.9 g/m², p = 0.666). Significantly reduced aortic area was observed in GHD (13.2 vs. 19.0 cm²/m², p = 0.001). This did not change with GH treatment. There were no differences in other LV parameters including end-diastolic volume index (EDVi), end-systolic volume index, stroke volume index (SVi), cardiac index and ejection fraction. There was a trend towards reduced baseline right ventricular (RV)SVi (44.1 vs. 49.1 ml/m², p = 0.0793) and increased RVEDVi over 1 year (70.3 vs. 74.3 vs. 73.8 ml/m², p = 0.062). Two patients demonstrated interstitial expansion, for example with fibrosis, and three myocardial ischaemia as assessed by late gadolinium enhancement and stress perfusion. The increased sensitivity of CMR to subtle cardiac changes demonstrates that adult-onset GHD patients have reduced aortic area and LVMi increases after 1 year of GH treatment. These early data should be studied in larger studies in the future.

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Variation in Vowel Duration Among Southern African American English Speakers.

Related Articles

Variation in Vowel Duration Among Southern African American English Speakers.

Am J Speech Lang Pathol. 2015 Aug;24(3):460-9

Authors: Holt YF, Jacewicz E, Fox RA

Abstract
PURPOSE: Atypical duration of speech segments can signal a speech disorder. In this study, we examined variation in vowel duration in African American English (AAE) relative to White American English (WAE) speakers living in the same dialect region in the South to characterize the nature of systematic variation between the 2 groups. The goal was to establish whether segmental durations in minority populations differ from the well-established patterns in mainstream populations.
METHOD: Participants were 32 AAE and 32 WAE speakers differing in age who, in their childhood, attended either segregated (older speakers) or integrated (younger speakers) public schools. Speech materials consisted of 14 vowels produced in hVd-frame.
RESULTS: AAE vowels were significantly longer than WAE vowels. Vowel duration did not differ as a function of age. The temporal tense-lax contrast was minimized for AAE relative to WAE. Vowels produced by females were significantly longer than vowels produced by males for both AAE and WAE.
CONCLUSIONS: African American speakers should be expected to produce longer vowels relative to White speakers in a common geographic area. These longer durations are not deviant but represent a typical feature of AAE. This finding has clinical importance in guiding assessments of speech disorders in AAE speakers.

PMID: 25951511 [PubMed - indexed for MEDLINE]

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Complexity markers in morphosyntactic productions in French-speaking children with specific language impairment (SLI).

Related Articles

Complexity markers in morphosyntactic productions in French-speaking children with specific language impairment (SLI).

Clin Linguist Phon. 2015;29(8-10):701-18

Authors: Prigent G, Parisse C, Leclercq AL, Maillart C

Abstract
The usage-based theory considers that the morphosyntactic productions of children with SLI are particularly dependent on input frequency. When producing complex syntax, the language of these children is, therefore, predicted to have a lower variability and to contain fewer infrequent morphosyntactic markers than that of younger children matched on morphosyntactic abilities. Using a spontaneous language task, the current study compared the complexity of the morphological and structural productions of 20 children with SLI and 20 language-matched peers (matched on both morphosyntactic comprehension and mean length of utterance). As expected, results showed that although basic structures were produced in the same way in both groups, several complex forms (i.e. tenses such as Imperfect, Future or Conditional and Conjunctions) were less frequent in the productions of children with SLI. Finally, we attempted to highlight complex linguistic forms that could be good clinical markers for these children.

PMID: 25774764 [PubMed - indexed for MEDLINE]

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Speech production in children with Down's syndrome: The effects of reading, naming and imitation.

Related Articles

Speech production in children with Down's syndrome: The effects of reading, naming and imitation.

Clin Linguist Phon. 2015;29(8-10):598-612

Authors: Knight RA, Kurtz S, Georgiadou I

Abstract
People with DS are known to have difficulties with expressive language, and often have difficulties with intelligibility. They often have stronger visual than verbal short-term memory skills and, therefore, reading has often been suggested as an intervention for speech and language in this population. However, there is as yet no firm evidence that reading can improve speech outcomes. This study aimed to compare reading, picture naming and repetition for the same 10 words, to identify if the speech of eight children with DS (aged 11-14 years) was more accurate, consistent and intelligible when reading. Results show that children were slightly, yet significantly, more accurate and intelligible when they read words compared with when they produced those words in naming or imitation conditions although the reduction in inconsistency was non-significant. The results of this small-scale study provide tentative support for previous claims about the benefits of reading for children with DS. The mechanisms behind a facilitatory effect of reading are considered, and directions are identified for future research.

PMID: 25774762 [PubMed - indexed for MEDLINE]

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Using ultrasound visual biofeedback to treat persistent primary speech sound disorders.

Related Articles

Using ultrasound visual biofeedback to treat persistent primary speech sound disorders.

Clin Linguist Phon. 2015;29(8-10):575-97

Authors: Cleland J, Scobbie JM, Wrench AA

Abstract
Growing evidence suggests that speech intervention using visual biofeedback may benefit people for whom visual skills are stronger than auditory skills (for example, the hearing-impaired population), especially when the target articulation is hard to describe or see. Diagnostic ultrasound can be used to image the tongue and has recently become more compact and affordable leading to renewed interest in it as a practical, non-invasive visual biofeedback tool. In this study, we evaluate its effectiveness in treating children with persistent speech sound disorders that have been unresponsive to traditional therapy approaches. A case series of seven different children (aged 6-11) with persistent speech sound disorders were evaluated. For each child, high-speed ultrasound (121 fps), audio and lip video recordings were made while probing each child's specific errors at five different time points (before, during and after intervention). After intervention, all the children made significant progress on targeted segments, evidenced by both perceptual measures and changes in tongue-shape.

PMID: 25751614 [PubMed - indexed for MEDLINE]

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Complete genome sequence of the novel duck hepatitis B virus strain SCP01 from Sichuan Cherry Valley duck

The duck hepatitis B virus (DHBV) strain, designated SCP01, was isolated and identified from a Sichuan Cherry Valley duck in Southwestern China. To determine the origination and evolution of this isolated stra...

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Complex multiple renal calculi: stone distribution, pelvicalyceal anatomy and site of puncture as predictors of PCNL outcome

Management of patients with complex multiple renal calculi has always remained challenging and they pose many difficulties during percutaneous nephrolithotomy (PCNL) like higher incidence of residual calculus ...

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Does laparoscopic transperitoneal simple nephrectomy for inflammatory and non-inflammatory kidneys differ?

Laparoscopic simple nephrectomy is the standard procedure for the removal of non-functioning benign kidney. It can be performed transperitoneally or retroperitoneally. There are several studies comparing the r...

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Neurotransmitters in hiccups

Hiccups are the sudden involuntary contractions of the diaphragm and intercostal muscles. They are generally benign and self-limited, however, in some cases they are chronic and debilitating. There are approx...

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Cost–effectiveness of apixaban and warfarin in the prevention of thromboembolic complications among atrial fibrillation patients

To reduce the risk of thromboembolic complications, clinical guidelines recommend anticoagulation treatment for almost all atrial fibrillation (AF) patients. Although warfarin has long been the primary treatme...

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Air ambulance co. employees forced to work seven-day shifts to keep jobs

SOUTH JORDAN, Utah — Former employees of the Air Medical Resource Group said they were forced by the company to work shifts lasting seven days or longer in order to keep their jobs.

AMRG, the parent company of Guardian Flight, Eagle Air Med and other air ambulance services, has been accused of putting its employees in unsafe conditions to avoid hiring additional personnel.

"No one should work seven days straight," former employee Dave Cavins told the Salt-Lake Tribune. "If you are on call 24-7, even after the third day, your mind won't be fully functional."

Cavins, who now works as a nurse, retired from the air ambulance service three years ago after the company kept forcing him to work long shifts under threat of termination.

"AMRG is the reason I got out," Cavins said. "I do not want to die on the job."

AMRG affiliates in other states have been criticized for similar practices.

Jeremiah Sappington, a North Dakota medic, quit two years ago after being forced to fly in bad weather and being assigned a medical director who was frequently out of town and rarely available to call.

In Hawaii, pilot James Stone was fired in 2010 for voicing concerns about his company's safety standards. In July 2016, Stone was awarded over $760,000 for his wrongful termination.

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Reconstruction of facial soft tissue: comparison between conventional procedures and the face-lift technique

Publication date: Available online 17 August 2016
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): A.K. Bartella, M. Ghassemi, F. Hölzle, A. Ghassemi
We compared the result of replacement using a modified face-lift technique with those of other commonly used surgical techniques for the treatment of defects of the soft tissue of the infraorbital and cheek region. We made a retrospective observational study of 86 patients who had defects of the facial soft tissue after excision of malignant tumours. Procedures used for reconstructions included non-vascularised skin grafts, local flaps, facelift technique, and microvascular free flaps, and we evaluated morbidity; duration of hospital stay; the need for, and duration of stay in, the intensive care unit (ICU); and functional and aesthetic outcomes.We studied 46 men and 40 women (mean (range) age 71 (8-99) years). We found no significant difference between the methods apart from shorter duration of hospital stay and lower incidence of ectropion in the facelift group. The facelift technique also gave the best aesthetic outcome. However, in defects larger than 60cm², microvascular free tissue transfer was the only choice. The facelift technique is reliable and safe, and gives excellent aesthetic and functional outcomes, but its use is limited to defects smaller than 60cm².



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Testing for ROS1 in non-small cell lung cancer: a review with recommendations

Abstract

Rearrangements of the ROS1 gene occur in 1–2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

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Self-Care in the Twenty First Century: A Vital Role for the Pharmacist

Abstract

In order for the global healthcare system to remain sustainable, healthcare spending needs to be reduced, and self-treating certain conditions under the guidance of a pharmacist provides a means of accomplishing this goal. This article was developed to describe global healthcare trends affecting self-care with a specific focus on the role of the pharmacist in facilitating over-the-counter (OTC) medication management. Potential healthcare-related economic benefits associated with the self-care model are outlined. The importance of the collaboration between healthcare providers (HCPs), including specialists, primary care providers, and pharmacists, is also discussed. The evolving role of the pharmacist is examined and recommendations are provided for ways to successfully engage with other HCPs and consumers to optimize the pharmacist's unique qualifications and accessibility in the community. Using the management of frequent heartburn with an OTC proton-pump inhibitor as a model, the critical role of the pharmacist in patient self-treatment of certain symptoms will be discussed based on the World Gastroenterology Organization's recently published guidelines for the community-based management of common gastrointestinal symptoms. As the global healthcare system continues to evolve, self-care is expected to have an increasing role in treating certain minor ailments, and pharmacists are at the forefront of these changes. Pharmacists can guide individuals in making healthy lifestyle choices, recommend appropriate OTC medications, and educate consumers about when they should consult a physician.

Funding: Pfizer Inc.

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A Systematic Review and Network Meta-Analysis to Evaluate the Comparative Efficacy of Interventions for Unfit Patients with Chronic Lymphocytic Leukemia

Abstract

Introduction

Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients.

Methods

For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL.

Results

In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints).

Conclusion

G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL.

Funding

F. Hoffmann-La Roche Ltd.

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Extracellular Vesicles in Glioblastoma: Role in Biological Processes and in Therapeutic Applications.

Extracellular Vesicles in Glioblastoma: Role in Biological Processes and in Therapeutic Applications.

Curr Cancer Drug Targets. 2016 Aug 13;

Authors: Giusti I, Di Francesco M, Dolo V

Abstract
Glioblastoma is the most common and most malignant form of primary brain cancer and it is characterized by one of the highest mortality among human cancers. Maximal and aggressive surgical resection is the first approach treatment but it is not usually definitive, being the tumor characterized by a high proliferative rate and an extensive invasion. An early diagnosis, associated to a careful monitoring, is pivotal in glioblastoma treatment; the Magnetic Resonance Imaging is used for monitoring purpose, but it's not sensitive enough to detect very small tumors; a valid alternative could be a repeated biopsy, but it is associated to a significant morbidity: less invasive options for diagnosis and therapeutic monitoring are unfailingly researched. In recent years it has begun to take hold the knowledge that glioblastoma cells secrete in their surrounding microenvironment extracellular vesicles (microvesicles and exosomes), which mirror the molecular features of parental cells and are able to escape from tumor microenvironment and reach cerebrospinal fluid and systemic blood circulation. Such information led to consider the possibility to use extracellular vesicles in biological fluids as markers of glioblastoma pathology and to use them as a more feasible "liquid-biopsy" to gain diagnostic information, follow the disease progression and the response to clinical treatment, just through a blood test or cerebrospinal fluid collection. To date the most interesting extracellular vesicles-associated molecules studied as glioblastoma markers include several miRNAs, EGFRvIII and IDH1R132H. Approaches aiming to use extracellular vesicles as cell-free vaccines or vehicle of therapeutic molecules are also taken into account.

PMID: 27528364 [PubMed - as supplied by publisher]

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New approaches in glioblastoma multiforme: the potential role of immune-check point inhibitors.

New approaches in glioblastoma multiforme: the potential role of immune-check point inhibitors.

Curr Cancer Drug Targets. 2016 Aug 13;

Authors: De Felice F, Musio D, Cassese R, Gravina GL, Tombolini V

Abstract
BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent brain tumor. Despite recent advances in treatment approaches the prognosis remains poor, with a median overall survival of 14.6 months. Immunotherapy is the subject of ongoing research and its benefit is becoming evident in other malignancies. Immune check-points such as cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed cell death receptor (PD-1) and indoleamine 2,3-dioxygenase (IDO) reduce immune response.
OBJECTIVE: To clarify the role of immune check point inhibitors in GBM management.
METHODS: Preclinical and clinical trials of immune check-point inhibitors in GBM were obtained by searching for English peer-reviewed articles on PubMed databases, trials registered on clincaltrials.gov and abstracts recently presented at international congresses.
RESULTS: Immune check point inhibitors may be of critical importance for the design of future immunotherapy approaches in GBM management.
CONCLUSION: Immune check-point inhibitors should be considered a promising treatment option in GBM.

PMID: 27528363 [PubMed - as supplied by publisher]

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New perspectives in glioblastoma: Nanoparticles-based approaches.

New perspectives in glioblastoma: Nanoparticles-based approaches.

Curr Cancer Drug Targets. 2016 Aug 13;

Authors: Luciano R, Saracino R, Battafarano G, Perrotta A, Manco M, Muraca M, Del Fattore A, Rossi M

Abstract
Glioblastoma multiforme represents one of the most aggressive tumor of central nervous system. Current therapy includes surgery, radiation and chemotherapy. These treatments are rarely curative and glioma are associated with a poor prognosis. Nanomedicine represents the most innovative branch of medicine since many studies demonstrated great advantage in the diagnosis and therapy of several diseases. In this review we will summarize the results obtained by the use of nanoparticles and extracellular vesicles in glioblastoma. A great interest is raising from these studies that underlined the efficacy and specificity of this treatment for glioma, reducing side-effects associated with conventional therapies.

PMID: 27528362 [PubMed - as supplied by publisher]

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Exploiting Microglial Functions for the Treatment of Glioblastoma.

Exploiting Microglial Functions for the Treatment of Glioblastoma.

Curr Cancer Drug Targets. 2016 Aug 13;

Authors: Russo CD, Lisi L, Tentori L, Navarra P, Graziani G, Combs CK

Abstract
Glioblastoma is the most common brain tumor in adults and is associated with a very low survival rate. The heterogeneity of the tumor microenvironment, its resistance to drug and radiation therapy, and its robust invasiveness all contribute to the poor outcome. Large numbers of glioma associated microglia and macrophages can accumulate within the tumor where they appear to have a role in prognosis. This has stimulated considerable interest in understanding the contribution of these cells to disease progression. Deciphering this biology has been complicated by the fact that these cells are a mixture of brain resident microglia as well as blood-derived macrophages with a spectrum of phenotypes that are likely dependent upon disease stage, tumor location, microenvironment, and perhaps even brain region. Nevertheless, promising preclinical studies suggest that stimulating glioma-associated microglia and macrophages to acquire an M1 anti-tumor phenotype or limiting their recruitment to the tumor microenvironment and the extent of M2 polarization are promising therapeutic strategies for the treatment of glioblastoma. We review not only the heterogeneous contribution of these cells to glioblastoma progression but also recent studies supporting the notion that they are viable therapeutic targets.

PMID: 27528361 [PubMed - as supplied by publisher]

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Malignant glioma in vitro models: On the utilization of stem-like cells and the recapitulation of molecular subtypes.

Malignant glioma in vitro models: On the utilization of stem-like cells and the recapitulation of molecular subtypes.

Curr Cancer Drug Targets. 2016 Aug 13;

Authors: Balvers R, Dirven CM, Leenstra S, Lamfers ML

Abstract
Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors after conventional treatment. The advent of selective cell culture protocols for the propagation of patient-derived glioma stem-like cells (GSCs) provides researchers the ability to selectively study the cells that could be at the root of tumor proliferation and resistance to therapy. As these techniques are widely applied in contemporary studies and becoming the preferred in vitro model, molecular characterization of GSCs is considered pivotal for the identification and advancement of novel therapies for this devastating disease. This review aims to provide an overview of canonical molecular alterations defining subtypes of malignant glioma as derived from genotypic, transcriptomic and epigenetic profiling in relation to their representation in GSC models. The distribution of these hallmark alterations as found in characterization studies of GSCs is compared between publications. Finally, conclusions of these studies with respect to coverage of driving alterations and translational relevance are provided. By doing so, we provide a contemporary overview of scientific results derived from GSC models and hopefully create appreciation of the advantages and caveats of utilizing these models for studying malignant glioma.

PMID: 27528360 [PubMed - as supplied by publisher]

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A Simple, Low-cost, and Robust System to Measure the Volume of Hydrogen Evolved by Chemical Reactions with Aqueous Solutions

The study of methods to generate on-demand hydrogen for fuel cells continues to grow in importance. However, systems to measure hydrogen evolution from the reaction of chemicals with water can be complicated and expensive. This article details a simple, low-cost, and robust method to measure the evolution of hydrogen gas.

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Firefighter Paramedic - City of Downey

DOWNEY, CITY OF 11111 BROOKSHIRE AVENUE DOWNEY, CALIFORNIA 90241 Updated: August 17, 2016 Job Classification: Firefighter/Paramedic The City of Downey is currently hiring for Firefighter/Paramedic. All testing must be completed by September 7, 2016. For more information about the job position and requirements, please visit http://ift.tt/2bds8gh. Please DO NOT call the City ...

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Heterogeneous clinical spectrum of interstitial lung disease in patients with anti-EJ anti-synthetase syndrome: a case series

Abstract

Auto-antibodies against aminoacyl-tRNA-synthetases (anti-ARS Abs) represent the hallmark of the anti-synthetase syndrome that is defined as the clinical association of fever, Raynaud's phenomenon, myositis, interstitial lung disease (ILD), arthritis and mechanic's hands. Recently, differences in clinical features depending on specific anti-ARS Abs have been reported. We describe three cases of anti-EJ (anti-glycyl) antibody-positive patients presenting with ILD as a common feature, but with heterogeneous histopathological and radiographic patterns and with different responses to treatment. Relapsing-remittent fever, refractory muscle involvement and seronegative arthritis were also striking clinical manifestations.

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A complex role of anthrax toxin receptor 2 polymorphisms and capillary morphogenesis protein 2 in ankylosing spondylitis pathogenesis

Abstract

This study investigated the role of anthrax toxin receptor 2 (ANTXR2) gene polymorphisms and capillary morphogenesis protein 2 (CMG2) expression in susceptibility and pathogenesis to ankylosing spondylitis (AS) in the Han Chinese in Beijing. A case-control study was performed using 602 AS patient samples meeting the revised New York criterion and 619 matched controls from Han Chinese individuals. Nineteen single-nucleotide polymorphisms (SNPs) of ANTXR2 genes were selected and genotyped using the Sequenom iPlex platform. Real-time polymerase chain reaction and flow cytometry were performed to investigate the impact of SNP polymorphisms on ANTXR2 transcription and CMG2 expression, respectively. The association of variants with AS was examined with UNPHASED 3.1.5. A novel association was observed between AS and three SNPs in the ANTXR2 gene (rs4690127, rs6823031, and rs4333130; P = 0.004, 0.011, and 0.013, respectively), confirming the association between rs433130 and AS in the Han Chinese. The strongest haplotype association was observed with rs4690127-rs6823031-rs4333130 (P = 2.5 × 10⁻⁴). rs6534639 and rs4333130 showed a cis-interaction (P = 0.027) in AS. ANTXR2 messenger RNA (mRNA) expression was significantly higher in the AS group than in the control group (P = 0.039). CMG2 expression in the lipopolysaccharide (LPS)-stimulated group was significantly lower than that in the control group (P = 0.018). This study reports a novel association between ANTXR2 and AS in the Han Chinese. ANTXR2 genetic polymorphisms affect ANTXR2 mRNA transcription and CMG2 expression. The opposing results observed for ANTXR2 transcription and CMG2 expression suggest a complex role of ANTXR2 polymorphisms in AS pathogenesis.

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Dermatomyositis in Joseph Wright’s 1768 painting of the air pump experiment

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Plantar forefoot pressures in psoriatic arthritis-related dactylitis: an exploratory study

Abstract

Dactylitis is a common feature of psoriatic arthritis (PsA); local physical trauma has been identified as a possible contributing factor. The aim of this study was to explore differences in forefoot plantar pressures in patients with PsA with and without dactylitis and compare to healthy controls. Thirty-six participants were recruited into three groups: group A PsA plus a history of dactylitis; group B PsA, no dactylitis; group C control participants. Forefoot plantar pressures were measured barefoot and in-shoe at the left second and fourth toes and corresponding metatarsophalangeal joints. Temporal and spatial parameters were measured and data from the foot impact scale for rheumatoid arthritis (FIS-RA), EQ5D and health assessment questionnaire (HAQ) were collected. Pressure time integral peak plantar pressure, and contact time barefoot and in-shoe were not significantly different between groups. Temporal and spatial parameters reported no significant differences between groups. ANOVA analysis and subsequent post hoc testing using Games-Howell test yielded significance in FIS-RA scores between both PsA groups versus controls, A p ≤ 0.0001 and PsA group B p < 0.0001 in the FIS-RA impairment and footwear domain, PsA group A p < 0.03 and PsA group B p ≤ 0.05 in the FIS-RA activity and participation domain compared to controls. This is the first exploratory study to investigate forefoot plantar pressures in patients with and without historical dactylitis in PsA. FIS-RA scores indicate PsA patients have significant limitations compared to controls, although a history of dactylitis does not appear to worsen patient reported outcomes.

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Letter to the Editor: “Comparison of efficacy of kinesiological taping and subacromial injection therapy in subacromial impingement syndrome”

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The A 3 adenosine receptor (A 3 AR): therapeutic target and predictive biological marker in rheumatoid arthritis

Abstract

The Gi protein-associated A₃ adenosine receptor (A₃AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A₃AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A₃AR may be utilized as a predictive biomarker. The A₃AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population.

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Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis

Abstract

Patients with ankylosing spondylitis (AS) reportedly have a higher mortality and morbidity risk. Osteoprotegerin (OPG) was recently defined as an important cardiovascular (CV) marker in the general population. We aimed to assess the relationship of serum OPG levels with arterial stiffness, carotid intima media thickness (CIMT), and clinical and laboratory data in AS patients. We examined 60 AS patients without CV disease or risk factors and 50 healthy controls. Disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), whereas functional capacity was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Serum OPG levels were measured with the enzyme-linked immunosorbent assay. Carotid-femoral pulse wave velocity (PWV) was used as an indicator of arterial stiffness, whereas CIMT (examined via carotid ultrasonography) was used to evaluate preclinical atherosclerosis. The mean serum OPG level, PWV, and CIMT were significantly higher in AS patients than in controls (106.7 ± 50.9 vs. 58.1 ± 12.7 pg/mL; 7.4 ± 1.8 vs. 6.2 ± 1.2 m/s; 0.72 ± 0.13 vs. 0.57 ± 0.07 mm, respectively; P < 0.001 for all). In AS patients, the serum OPG levels were not significantly correlated with PWV and CIMT but were significantly correlated with erthrocyte sedimentation rate, BASFI, and ASDAS. AS patients without CV disease or risk exhibited high OPG levels and increased PWV and CIMT values. Although OPG levels were not significantly correlated with PWV or CIMT, future long-term follow-up studies will help define the predictive value of OPG in these patients.

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Politics, culture, and the legitimacy of disease: the case of Buerger’s disease

Abstract

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

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GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis

Abstract

The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA.

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Is late-onset disease or the lower rate of M694V mutations associated with the mild disease phenotype?

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Immunosuppressive treatment for pure membranous lupus nephropathy in a Hispanic population

Abstract

Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19–16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08–5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010–1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.

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Fast 1.5 T chest MRI for the assessment of interstitial lung disease extent secondary to systemic sclerosis

Abstract

This study aims to evaluate the utility of magnetic resonance imaging (MRI) to assess interstitial lung disease (ILD) extent in patients with systemic sclerosis (SSc). Patients with SSc and varying degrees of ILD with a high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and a chest MRI containing an ultrafast SE sequence performed less than 1 year apart were included in the study. Wells global disease extent and Goh's staging algorithm were used to measure and categorize ILD both for MRI and HRCT. Correlation and diagnostic performance of MRI compared with HRCT and PFTs were calculated. Eighteen SSc patients were studied. MRI showed a good performance to detect ILD (AUC = 0.96) and was correlated with forced vital capacity (r = −0.60, p = 0.01), diffusing capacity of the lung for carbon monoxide (r = −0.79, p = 0.04), and also with HRCT (r = 0.85, p < 0.001), but MRI extent values were consistently lower than HRCT and, thus, not directly comparable. Goh's algorithm using HRCT and transformed to be used with MRI showed a good agreement (kappa = 0.73, p < 0.001) and MRI-measured ILD extent presented good intra-observer (ICC = 0.86) and inter-observer (ICC = 0.90) reliability. In SSc patients, MRI proved to be a good technique to detect and categorize ILD extent compared with HRCT, suggesting that it may be a valuable x-ray sparing technique for selected cases.

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Reliability of heart period and systolic arterial pressure variabilities in women with fibromyalgia syndrome

Abstract

The aim of this study is to define absolute and relative reliability of spectral indices of cardiovascular autonomic control in the supine position in women with fibromyalgia syndrome (FMS). Twenty-three women with FMS (age 48 ± 7 years) took part in the study. ECG, finger blood pressure, and respiration were continuously recorded in all participants at rest in baseline 1 (BL1) and after 15 days from BL1 (BL2). The power spectrum analysis provided two oscillatory components: low frequency (LF, 0.04–0.15 Hz) and high frequency (HF, 0.15–0.4 Hz) from the heart period (HP) variability and the LF oscillatory component from SAP variability (LF_SAP). Absolute and relative reliability were rated by 95 % of the limit of random variation and intraclass correlation coefficient (ICC), respectively. No significant differences were observed between BL1 and BL2 for the spectral indices of HP and SAP variabilities. The 95 % limit of the random variation of these indices indicated that the values of repeated measurements were between 22 % higher and 0.2 % lower (more reliable parameter; average of HP variability) and 912.9 % higher and 0.2 % lower (less reliable parameter; LF_SAP) than BL1. Conversely, the index of relative reliability (ICC) ranged from 0.23 to 0.70 indicating a good reliability. The spectral indices of cardiovascular autonomic control in women with FMS seem to present good relative reliability. Therefore, these indices can be useful as parameters to quantify if a variation was consistent and accurate in the retest besides adding crucial information for clinical research and clinical evaluation of FMS patients.

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A randomized, controlled trial of efficacy and safety of Anbainuo, a bio-similar etanercept, for moderate to severe rheumatoid arthritis inadequately responding to methotrexate

Abstract

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group—significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P < 0.001, P = 0.002). The ACR-N was 2.85 ± 6.73 vs. −3.24 ± 8.78 % in the control group (P < 0.001). During the first 12 weeks of treatment, 66 adverse events (AE) were reported in the Anbainuo group (15.6 %) and 21 AEs (10.5 %) occurred in the control group, whereby the rate of the Anbainuo group was slightly higher than the control group (P = 0.042). Severe adverse events (SAEs) occurred in the Anbainuo group (1.3 %) and one (SAE) occurred in the control group (0.5 %) (P = 0.19). Anbainuo displays a rapid onset of efficacy as well as good tolerance and safety in MTX-IR patients having moderate to severe RA.

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Magnetic stimulation of the upper trapezius muscles in patients with migraine - A pilot study.

Magnetic stimulation of the upper trapezius muscles in patients with migraine - A pilot study.

Eur J Paediatr Neurol. 2016 Aug 1;

Authors: Sollmann N, Trepte-Freisleder F, Albers L, Jung NH, Mall V, Meyer B, Heinen F, Krieg SM, Landgraf MN

Abstract
BACKGROUND: Repetitive peripheral magnetic stimulation (rPMS) has been applied to musculoskeletal pain conditions. Since recent data show that migraine and tension-type headache (TTH) might be closely related to peripheral muscular pain in the neck and shoulder region (supporting the concept of the trigemino-cervical complex (TCC)), this pilot study explores the acceptance of rPMS to the upper trapezius muscles in migraine (partly in combination with TTH).
METHODS: We used rPMS to stimulate active myofascial trigger points (aTrPs) of the upper trapezius muscles in 20 young adults suffering from migraine. Acceptance was assessed by a standardized questionnaire, whereas self-rated effectiveness was evaluated by headache calendars and the Migraine Disability Assessment (MIDAS). Algometry was performed to explore the local effect of rPMS on the muscles.
RESULTS: Acceptance of rPMS was shown in all subjects without any adverse events, and rPMS had a statistically significant impact on almost every parameter of the headache calendar and MIDAS. Among others, the number of migraine attacks (p < 0.001) and migraine intensity (p = 0.001) significantly decreased regarding pre- and post-stimulation assessments. Accordingly, 100.0% of subjects would repeat the stimulation, while 90.0% would recommend rPMS as a treatment option for migraine.
CONCLUSIONS: rPMS might represent a promising tool to alleviate migraine symptoms within the context of myofascial pain. This might be due to stimulation-dependent modulation of the peripheral sensory effect within the TCC in migraine. However, sham-controlled studies with larger and more homogeneous cohorts are needed to prove a potential beneficial effect. Ethics Committee Registration Numbers: 356-14 and 447/14.

PMID: 27528122 [PubMed - as supplied by publisher]

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Transcanal Micro-Osteotome Only Technique for Excision of Exostoses.

Related Articles

Transcanal Micro-Osteotome Only Technique for Excision of Exostoses.

Otol Neurotol. 2016 Feb;37(2):185-9

Authors: Ghavami Y, Bhatt J, Ziai K, Maducdoc MM, Djalilian HR

Abstract
OBJECTIVES: To evaluate the outcomes and complications of transcanal excision of exostoses using micro-osteotomes, without a postauricular incision or the use of the drill.
STUDY DESIGN: A retrospective chart review of patients undergoing exostoses excision.
SETTING: Tertiary Care Medical Center.
SUBJECTS AND METHODS: All of the patients underwent surgical removal of the exostoses using only a 1 or 2 mm micro-osteotomes. Patients were followed postoperatively and associated complications were evaluated.
RESULTS: One-hundred thirty-eight ears in 106 patients were treated for obstructive exostosis. The average age of patients was 43 ± 16 years. Of these, 99 were man (93%) and 7 were woman (7%). A majority of the patients (84%, n = 89) had 90 to 100% obstruction of the ear canal. Complete ear canal healing was observed in 80% of patients by 3 weeks. All but one patient had healed by 6 weeks postoperatively. There were 9 (6.5%) slit tympanic membrane perforations that healed with intraoperative gelfoam or fascia myringoplasty. One patient had an anterior canal mobilization which required Xeroform packing for 3 weeks for stabilization. There were no postoperative vertigo, facial paresis, conductive/sensorineural hearing loss, soft tissue stenoses, and no skin grafting required.
CONCLUSIONS: This is the first study to report a series of patients performing solely a transcanal approach using micro-osteotomes for removing exostoses. Results indicate that it is a safe procedure with low complication rate and expeditious healing. Patients with 100% obstruction can have this procedure performed with no significant increase in morbidity.

PMID: 26669556 [PubMed - indexed for MEDLINE]

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Pancreaticoduodenectomy in patients with type 1 Neurofibromatosis: Report of two cases and literature review.

Pancreaticoduodenectomy in patients with type 1 Neurofibromatosis: Report of two cases and literature review.

Int J Surg Case Rep. 2016 Aug 11;27:36-40

Authors: Teixeira F, Menegozzo CA, Couto Netto SD, Scapini G, Akaishi EH, Vasconcelos MP, Utiyama EM

Abstract
INTRODUCTION: Type 1 Neurofibromatosis (NF1) is one of the most common autosomal dominantly inherited multisystem disorders. It is associated with an increased risk of developing neurologic and gastrointestinal (GI) malignant neoplasms. The incidence of GI involvement is reported in 10-25% of patients. Less than 5% of NF1 patients with GI neoplasms manifest symptoms. The presence of synchronic gastrointestinal stromal and neuroendocrine tumors is rare in these patients.
PRESENTATION OF CASES: The first case is a 37 year-old male patient with a history of abdominal pain for a few months. Imaging study showed a periampullary mass and a solid lesion at the third duodenal portion. He was submitted to a pancreatoduodenectomy and histological anaylisis showed two low-grade neuroendocrine tumors and a gastrointestinal stromal tumor. The second case is a 47 year-old female patient with a routine computed tomography scan showing a duodenal and a jejunal lesion. Duodenopancreatectomy was performed and histological analysis showed a neuroendocrine adenocarcinoma of the duodenum and two jejunal lesions compatible with GI tumors.
DISCUSSION: GI symptoms such as jaundice, pain and bleeding in NF1 patients should prompt urgent admission Occasionally, associated gastrointestinal tumors may be incidentally found in asymptomatic NF1 patients. The presence of a periampullary or duodenal neoplasia such as neuroendocrine tumors should be evaluated.
CONCLUSION: Although rare, the synchronic presentation of gastrointestinal tumors in patients with NF1 should be ruled out since it can lead to higher morbidity and mortality rates. Single-stage surgical management is feasable and yields satisfactory results.

PMID: 27529834 [PubMed - as supplied by publisher]

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Microwave ablation of liver metastasis complicated by Clostridium perfringens gas-forming pyogenic liver abscess (GPLA) in a patient with past gastrectomy.

Microwave ablation of liver metastasis complicated by Clostridium perfringens gas-forming pyogenic liver abscess (GPLA) in a patient with past gastrectomy.

Int J Surg Case Rep. 2016 Aug 11;27:32-35

Authors: Kyang LS, Bin Traiki TA, Alzahrani NA, Morris DL

Abstract
INTRODUCTION: Gas-forming pyogenic liver abscess (GPLA) caused by C. perfringens is rare but fatal. Patients with past gastrectomy may be prone to such infection post-ablation.
PRESENTATION OF CASE: An 84-year-old male patient with past gastrectomy had MW ablation of his liver tumors complicated by GPLA. Computerised tomography scan showed gas-containing abscess in the liver and he was managed successfully with antibiotic and percutaneous drainage of the abscess.
DISCUSSION: C. perfringens GPLA secondary to MW ablation in a patient with previous gastrectomy has not been reported in the literature. Gastrectomy may predispose to such infection. Even in high-risk patients, empirical antibiotic before ablation is not a standard of practice. Therefore following the procedure, close observation of patients' conditions is necessary to allow early diagnosis and intervention that will prevent progression of infection.
CONCLUSION: Potential complication of liver abscess following MW ablation can never be overlooked. The risk may be enhanced in patients with previous gastrectomy. Early diagnosis and management may minimise mortality and morbidity.

PMID: 27529833 [PubMed - as supplied by publisher]

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The Use of Complementary and Alternative Medicine Supplements of Potential Concern during Breast Cancer Chemotherapy.

The Use of Complementary and Alternative Medicine Supplements of Potential Concern during Breast Cancer Chemotherapy.

Evid Based Complement Alternat Med. 2016;2016:4382687

Authors: Sweet E, Dowd F, Zhou M, Standish LJ, Andersen MR

Abstract
Objective. While many Complementary and Alternative Medicines (CAM) are unlikely to interact negatively with conventional oncology treatment, some ingestible CAM substances have biological activities that may reduce the effectiveness of chemotherapy or radiation. This study surveyed women with breast cancer in order to document the extent to which women with breast cancer use these CAM substances of concern concurrently with conventional treatments. Methods. A total of 398 women completed a survey describing their use of CAM at various time points in their cancer treatment. This report focuses on a subsample of 250 women receiving chemotherapy or radiation who reported using specific one or more of several chemotherapies. Results. Of those participating, 104 (43.7%) of those receiving chemotherapy (n = 238) and 45 (32.3%) of those receiving radiation (139; 58.4% of all patients) reported using one or more CAM substances that could be cause for concern when taken concurrently. Conclusion. Research is needed to understand the real risks associated with CAM and conventional polypharmacy. If risks associated with CAM conventional polypharmacy use prove to be substantial then improved systems to assure all women get advice regarding herb and supplement use during breast cancer treatment appear to be needed.

PMID: 27528880 [PubMed]

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Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries.

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Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries.

J Steroid Biochem Mol Biol. 2016 May;159:73-85

Authors: Dikshit A, Gao C, Small C, Hales K, Hales DB

Abstract
Flaxseed has been studied for decades for its health benefits that include anti-cancer, cardio-protective, anti-diabetic, anti-inflammatory properties. The biologically active components that mediate these effects are the omega-3 fatty acids and the lignan, secoisolariciresinol diglucoside. We have previously shown that whole flaxseed supplemented diet decreases the severity and incidence of ovarian cancer while a 15% dose of flaxseed is most protective against inflammation and estrogen-induced chemical and genotoxicity. The objective of this study was to dissect the independent effects of the two flaxseed components on estrogen signaling and metabolism. Two and half year old hens were fed either a control diet, 15% whole flaxseed diet, defatted flax meal diet or 5% flax oil diet for 3 months after which the animals were sacrificed and blood and tissues were harvested. Whole flaxseed diet caused a decrease in expression of ERα. ERα target gene expression was assessed using RT(2) profiler PCR array. Some targets involved in the IGF/insulin signaling pathway (IRS1, IGFBP4, IGFBP5) were downregulated by flaxseed and its components. Flaxseed diet also downregulated AKT expression. A number of targets related to NF-kB signaling were altered by flaxseed diet including a series of targets implicated in cancer. Whole flaxseed diet also affected E2 metabolism by increasing CYP1A1 expression with a corresponding increase in the onco-protective E2 metabolite, 2-methoxyestradiol. The weak anti-estrogens, enterolactone, enterodiol and 2-methoxyestradiol, might be working synergistically to generate a protective effect on the ovaries from hens on whole flaxseed diet by altering the estrogen signaling and metabolism.

PMID: 26925929 [PubMed - indexed for MEDLINE]

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A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

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A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

J Int Soc Sports Nutr. 2015;12:36

Authors: Lehnen TE, da Silva MR, Camacho A, Marcadenti A, Lehnen AM

Abstract
Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.

PMID: 26388708 [PubMed - indexed for MEDLINE]

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