The effect of alphaMSH analogues on rat bones

Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor-alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and [(6)Asn]alphaMSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC(50) of [(6)His]alphaMSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 +/- 0.0045, 1.523 +/- 0.707, 0.780 +/- 0.405, and 250.320 +/- 42.234 nM, respectively, and the EC(50) of [(6)Asn]alphaMSH-ND were 16.8 +/- 6.94, 271.8 +/- 21.95, 8.0 +/- 1.21, and 1132.5 +/- 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [(6)His]alphaMSH-ND and the [(6)Asn]alphaMSH-ND treated groups (346.0 +/- 20.63 g vs. 350.0 +/- 13.57 g) were lower than that of the vehicle treated group (375.8 +/- 17.31 g, p < 0.05). There was no difference in the total femoral BMD measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss was found after treatment of the alphaMSH analogues peripherally.     

Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

Use of N-butyl cyanoacrylate in the successful transcatheter arterial embolization of an arteriovenous fistula caused by blunt pelvic fracture: A case report and review of literature

Rationale:Traumatic arteriovenous fistulas (AVFs) of the pelvis are uncommon and present with a variety of clinical manifestations; their detection may be difficult. An endovascular approach is usually the first choice of treatment, because surgical intervention is complicated due to the location of the lesions.Patient concerns:A 68-year-old man was admitted with severe pelvic pain following a fall.Diagnosis:A pelvic bone fracture (Young and Burgess Classification, lateral compression type II) was revealed on pelvic computed tomography (CT), while a pelvic sidewall hematoma, unaccompanied by any vascular injury, was detected on multidetector CT.Interventions:Pelvic angiography revealed an AVF between the internal iliac artery and vein, which was undetected by MDCT. The AVF was successfully treated using transcatheter arterial embolization (TAE) with n-butyl cyanoacrylate (NBCA).Outcomes:The patient recovered well and was discharged 4 weeks later. No complications were noted at the 8-month follow-up.Lessons:AVF may occur as a complication of blunt pelvic bone fracture. A high index of suspicion, angiography, and prompt diagnosis resulted in the successful management of our patient who presented with risk factors. Furthermore, TAE using NBCA enables a minimally invasive and effective treatment of traumatic pelvic AVF.     

A New Asymmetric Directional Microphone Algorithm With Automatic Mode‐Switching Ability for Binaural Hearing Support Devices

For hearing support devices, it is important to minimize the negative effect of ambient noises for speech recognition but also, at the same time, supply natural ambient sounds to the hearing‐impaired person. However, conventional fixed bilateral asymmetric directional microphone (DM) algorithms cannot perform in such a way when the DM‐mode device and a dominant noise (DN) source are placed on the same lateral hemisphere. In this study, a new binaural asymmetric DM algorithm that can overcome the defects of conventional algorithms is proposed. The proposed algorithm can estimate the position of a specific DN in the 90°–270° range and switch directional‐ and omnidirectional‐mode devices automatically if the DM‐mode device and the DN are placed in opposite lateral hemispheres. Computer simulation and KEMAR mannequin recording tests demonstrated that the performance of the conventional algorithm deteriorated when the DM‐mode device and the DN were placed in the opposite hemisphere; in contrast, the performance of the proposed algorithm was consistently maintained regardless of directional variations in the DN. Based on these experimental results, the proposed algorithm may be able to improve speech quality and intelligibility for hearing‐impaired persons who have similar degrees of hearing impairment in both ears.     

An overview of hypertension and cardiac involvement in Asia: Focus on heart failure

Cardiovascular Disease (CVD) is the leading cause of deaths worldwide, contributing to about 30% of all deaths. Half of the cases of CVD are estimated in Asia, the world's most populous continent. Hypertension, a major modifiable risk factor for CVD, results in more deaths than any other CV risk factors in the Asian regions. The total number of patients with hypertension is likely to grow as the population ages. The proportion of the elderly population aged 65 years or more in Asia is expected to increase from 7.4% in 2015 to 10.9% in 2030. It is important to note that more than half (54%) of the world's population live in Asia. Aside of being the biggest single risk factor for global deaths, hypertension is also an important precursor and most common risk factor of heart failure (HF). An increase in HF prevalence is clearly related to the rapid epidemiological transition caused by changes in lifestyle in Asian countries. However, the availability of data on HF burden and health care delivery is limited in Asia compared with Europe and North America. This reality has driven the working group of Asian experts for example the HOPE Asia Network to concentrate on hypertension as risk factors for CVD, with the mission to improve the management of hypertension resulting in organ protection toward a goal of achieving “ZERO” CV event in Asia. This paper aims to give an overview regarding the heart problems caused by hypertension in Asia, focus on HF.     

Current status of ambulatory blood pressure monitoring in Asian countries: A report from the HOPE Asia Network

Ambulatory blood pressure monitoring (ABPM) can measure 24‐hour blood pressure (BP), including nocturnal BP and diurnal variations. This feature of ABPM could be of value in Asian populations for preventing cardiovascular events. However, no study has yet investigated regarding the use of ABPM in actual clinical settings in Asian countries/regions. In this study, 11 experts from 11 countries/regions were asked to answer questionnaires regarding the use of ABPM. We found that its use was very limited in primary care settings and almost exclusively available in referral settings. The indications of ABPM in actual clinical settings were largely similar to those of home BP monitoring (HBPM), that is, diagnosis of white‐coat or masked hypertension and more accurate BP measurement for borderline clinic BP. Other interesting indications, such as nighttime BP patterns, including non‐dipper BP, morning BP surge, and BP variability, were hardly adopted in daily clinical practice. The use of ABPM as treatment guidance for detecting treated but uncontrolled hypertension in the Asian countries/regions didn't seem to be common. The barrier to the use of ABPM was primarily its availability; in referral centers, patient reluctance owing to discomfort or sleep disturbance was the most frequent barrier. ABPM use was significantly more economical when it was reimbursed by public insurance. To facilitate ABPM use, more simplified indications and protocols to minimize discomfort should be sought. For the time being, HBPM could be a reasonable alternative.     

Diversity of and initiatives for hypertension management in Asia—Why we need the HOPE Asia Network

The Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network was set up to improve the management of hypertension in Asia with the ultimate goal of achieving “zero” cardiovascular events. Asia is a diverse continent, and the prevalence of hypertension has increased over the last 30 years. There are a number of Asia‐specific features of hypertension and hypertension‐related cardiovascular complications, which means that a region‐specific approach is needed. White‐coat hypertension will become more of an issue over time as Asian populations age, and masked hypertension is more prevalent in Asian than in Western countries. Identifying and treating masked hypertension is important to reduce cardiovascular risk. Abnormal patterns of blood pressure (BP) variability common in Asia include exaggerated early morning BP surge and nocturnal hypertension. These are also important cardiovascular risk factors that need to be managed. Home blood pressure monitoring (HBPM) is an important tool for detecting white‐coat and masked hypertension, and monitoring BP variability, and practices in Asia are variable. Use of HBPM is important given the Asia‐specific features of hypertension, and strategies are needed to improve and standardize HBPM usage. Development of HBPM devices capable of measuring nocturnal BP along with other information and communication technology‐based strategies are key developments in the widespread implementation of anticipation medicine strategies to detect and prevent cardiovascular events in patients with hypertension. Region‐wide differences in hypertension prevalence, control, and management practices in Asia highlight the importance of information sharing to facilitate best practices.     

Hypertension and the development of New onset chronic kidney disease over a 10 year period: a retrospective cohort study in a primary care setting in Malaysia

Background

Little is known about the rate of progression to chronic kidney disease (CKD) among hypertensive patients, particularly at the primary care level. This study aims to examine risk factors associated with new onset CKD among hypertensive patients attending a primary care clinic.

Methods

This is a 10-year retrospective cohort study of 460 patients with hypertension who were on treatment. Patient information was collected from patient records. CKD was defined as a glomerular filtration rate <60?ml/min per 1.73?m² (Cockcroft-Gault equation). Multiple logistic regression statistics was used to test the association in newly diagnosed CKD.

Results

The incidence of new CKD was 30.9% (n?=?142) with an annual rate of 3%. In multivariate logistic regression analysis, factors associated with development of new onset of CKD among hypertensive patients were older age (odds ratio [OR] 1.123, 95% confidence interval [CI] 1.078-1.169), presence of diabetes (OR 2.621, 95% CI 1.490-4.608), lower baseline eGFR (OR 1.041, 95% CI 0.943-0.979) and baseline hyperuricaemia (OR 1.004, 95% CI 1.001-1.007).

Conclusions

The progression to new onset CKD is high among urban multiethnic hypertensive patients in a primary care population. Hence every effort is needed to detect the presence of new onset CKD earlier. Hypertensive patients who are older, with underlying diabetes, hyperuricaemia and lower baseline eGFR are associated with the development of CKD in this population.

     

The Effects of Surgical Cytoreduction Prior to Imatinib Therapy on the Prognosis of Patients with Advanced GIST

Background

Baseline tumor size is one of important prognostic factors for imatinib therapy in patients with advanced gastrointestinal stromal tumor (GIST). The purpose of this study was to determine whether surgical cytoreduction before imatinib therapy can improve the prognosis.

Methods

A total of 249 patients with advanced GIST were reviewed retrospectively. Patients were categorized into two groups according to the degree of initial cytoreduction: 35 patients with ≥75 % of initial tumor bulk removed (cytoreduction group) and the other 214 patients (no cytoreduction group). The median follow-up was 44.0 months.

Results

Patients in the cytoreduction group were younger, in better performance, showed more initially metastatic disease, peritoneal metastases, but fewer liver metastases. The baseline tumor size when starting imatinib became significantly reduced in the cytoreduction group, which made significant difference between the two groups. By multivariate analyses, mutational status, tumor size, and granulocyte count at presentation were associated with progression-free survival. Age and tumor size were associated with overall survival. However, initial cytoreduction was not significantly related to the prognosis.

Conclusions

Cytoreduction before imatinib therapy appears not to improve the prognosis. Imatinib therapy should still represent the initial treatment for advanced GIST.