Clinical utility of an endoscopic ultrasound-guided rendezvous technique via various approach routes

Background

The endoscopic ultrasound-guided rendezvous techniques (EUS-rendezvous) provide reliable biliary access after failed endoscopic retrograde cholangiopancreatography (ERCP) cannulation. We evaluated the clinical utility of an EUS-rendezvous technique using various approach routes.

Methods

Patients undergoing EUS-rendezvous for biliary access after failed bile duct cannulation in ERCP were included. EUS-rendezvous was performed via three approach routes depending on the patient’s condition: transgastric, transduodenal in a short endoscopic position, or transduodenal in a long endoscopic position. The main outcomes were the technical success rates. Secondary outcomes were procedure time and complications.

Results

Fourteen patients (median age, 77 years) underwent EUS-rendezvous for biliary access resulting from failed biliary cannulation. The reasons for biliary drainage were malignant biliary obstruction in five patients and choledocholithiasis in nine. Transgastric, transduodenal in a short position, and transduodenal in a long position EUS-rendezvous was performed in five, five, and four patients, respectively. Bile duct puncture occurred in the left intrahepatic duct in four patients, right hepatic duct in one, middle common bile duct in four, and lower common bile duct in five. The technical success rate was 100 %. In four patients, the approach route was modified from transduodenal in a short position to transduodenal in a long position or transgastric route. The median procedure time was 81 min. One case each of biliary peritonitis and pancreatitis occurred and were managed conservatively.

Conclusions

EUS-rendezvous provided safe and reliable transpapillary bile duct access after failed ERCP cannulation. The selection of the appropriate approach routes, depending on patient condition, is critical.     

Decreased expression of aquaporin 2 in the collecting duct of mice lacking the vasopressin V1a receptor

Background

Vasopressin V1a receptor null (V1aR^?/?) mice recently showed incomplete urinary concentration due to higher urine volume during control and water diuresis (euhydration), but showed normal response during dehydration (Aoyagi et al., Am J Physiol 295: F100–7, 2008).

Methods

Water balance, plasma vasopressin, plasma and urine osmolality, and aquaporin 2 (AQP2) expression in the kidney of wild-type (WT) and V1aR^?/? mice were therefore further examined using improved methods of urine collection (urinary bladder urine).

Results

V1aR^?/? mice demonstrated a lower urine osmolality (3,360 ± 138 vs. 3,610 ± 47 mOsm/kgH₂O) and a higher plasma osmolality (354.3 ± 1.3 vs. 342.5 ± 1.5 mOsm/kgH₂O) after dehydration for 24 h compared to WT mice (P < 0.05). In contrast, the plasma vasopressin concentration was significantly (P < 0.001) higher in the V1aR^?/? mice (48.8 ± 4.8 vs. 22.1 ± 2.4 pg/ml). On the other hand, although the AQP2 protein expression in the kidney was increased after dehydration, the basal (control) and dehydration-induced AQP2 protein levels were significantly lower in V1aR^?/? mice compared to WT mice (by Western blotting). Staining by an anti-AQP2 antibody in the luminal membrane of the collecting ducts was increased in both V1aR^?/? and WT mice after dehydration, but was relatively weaker in the V1aR^?/? mice (by immunohistochemistry). Moreover, urinary excretion of AQP2 protein, an index of the luminal AQP2 expression, was significantly (P < 0.05) lower in the V1aR^?/? mice.

Conclusion

V1aR signaling may be fundamentally important for the expression of AQP2 in the collecting ducts during control conditions and dehydration.     

The mitochondrial protein frataxin is downregulated in hemodialysis patients

Background

The mitochondrial protein frataxin regulates iron metabolism for heme and iron sulfur cluster synthesis in the mitochondria and could be associated with the regulation of oxidative stress. To clarify the expression of frataxin and its association with uremia, we evaluated the mRNA and protein levels of frataxin in the polymorphonuclear leukocytes (PMNLs) of patients on hemodialysis (HD).

Methods

Uremic patients on HD (n = 18) and healthy control subjects (n = 18) were investigated. PMNLs were isolated by differential centrifugation. The mRNA levels of frataxin in isolated leukocytes were quantified by TaqMan real-time polymerase chain reaction. Frataxin protein expression in the cell lysate was evaluated using SDS-polyacrylamide gel electrophoresis and Western blotting.

Results

The frataxin/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in PMNLs from uremic patients was significantly lower than that in control subjects. Frataxin protein expression in uremic patients was also significantly lower than that in controls. Multiple regression analysis showed that frataxin mRNA levels were independently associated with the serum levels of both the oxidative stress marker malondialdehyde and the proinflammatory cytokine tumor necrosis factor-α.

Conclusion

The downregulation of frataxin seems to be linked with uremic status, which is usually associated with chronic inflammation and the acceleration of oxidative stress. Mitochondrial iron regulation may play a role in several comorbidities and in the poor prognosis in uremic patients. Further investigation is needed to elucidate whether reduced frataxin levels are linked to the pathological status of uremic patients and whether uremic substances affect frataxin expression.     

Effects of Nordic Walking Compared to Conventional Walking and Band-Based Resistance Exercise on Fitness in Older Adults

The purpose of this study was to compare the effects of Nordic walking with conventional walking and band-based resistance exercise on functional fitness, static balance and dynamic balance in older adults. Volunteers (n = 65) were divided into four groups: Nordic walking (NW), conventional walking (CW), resistance (RES), and control. Each group performed activity 50-70 min·day⁻¹ (warm-up 10-15 min, main exercise 30-40, and cool down 10-15 min), 3 days·week⁻¹ (NW and CW) or 2 day·week⁻¹ (RES) for 12 wks. Upper-body strength improved (p < 0. 05) in the RES (22.3%) and the NW (11.6%) groups compared to the CW and control groups. Cardio- respiratory fitness improved more in the NW (10.9%) and CW (10.6%) groups compared to the RES and control groups. Upper- and lower-body flexibility also improved in all exercise groups compared to the control group. There were no improvements in balance measures in any group. While all modes of exercise improved various components of fitness, Nordic walking provided the best well-rounded benefits by improving upper-body strength, cardiovascular endurance, and flexibility. Therefore, Nordic walking is recommended as an effective and efficient mode of concurrent exercise to improve overall functional fitness in older adults.

Key Points

• Nordic walking, conventional walking, and resistance training are beneficial for older adults.
• Nordic walking and conventional walking both improve cardio-respiratory fitness while resistance training does not.
• Nordic walking provides additional benefits in upper-body muscular strength compared to conventional walking.
• Nordic walking is an effective and efficient mode of exercise to improve overall fitness in older adults.

Key words: Walking, resistance exercise, concurrent exercise, aging, functional fitness     

Usefulness of right ventricular tissue Doppler imaging for diagnosis of right ventricular myocardial infarction

Background

Right ventricular myocardial infarction (RVMI) is a complication of acute inferior myocardial infarction and sometimes causes severe hemodynamic disturbance. It is therefore important to promptly detect RVMI and assess the severity of right ventricular (RV) dysfunction. Tissue Doppler imaging (TDI) is a useful method to assess left ventricular function and RV function. In this study, we investigated the possibility of diagnosing RVMI using tricuspid annular velocity determined by TDI.

Methods

Thirty consecutive patients with first acute inferior myocardial infarction were studied. The diagnosis of RVMI was based on an ST-segment elevation of at least 0.1 mV in lead V4R. The patients were classified into 12 patients with RVMI (the RVMI group) and 18 patients without RVMI (non-RVMI group). All patients underwent two-dimensional echocardiography, pulsed Doppler and TDI, and coronary angiography within 48 h after onset of myocardial infarction. Tricuspid inflow velocity was recorded by pulsed Doppler and early diastolic tricuspid inflow velocity (TVE) was measured. Peak early diastolic velocity of the tricuspid annulus (TVe’) at the RV free wall was recorded using TDI. The ratio of TVE to TVe’ (TVE/TVe’) was calculated.

Results

TVe’ was significantly lower in the RVMI group compared to that in the non-RVMI group (5.9 ± 1.3 vs. 9.1 ± 3.1; p = 0.0025). On the basis of a TVe’ cutoff value of less than 8.3 cm/s, RVMI was diagnosed with 100 % sensitivity and 61 % specificity.

Conclusions

The early diastolic tricuspid annular velocity determined by TDI is a noninvasive and sensitive index for diagnosing RVMI.     

Inhibitory effects of IL-12 on experimental tooth movement and root resorption in mice

ObjectiveInterleukin (IL)-12 is an important cytokine for innate and adaptive immunity. We previously reported that IL-12 inhibits tumour necrosis factor (TNF)-α-mediated osteoclast formation by inducing apoptosis. We also reported that TNF-α plays an important role in mechanical loading-induced osteoclast formation and bone resorption during orthodontic tooth movement. In this study, we investigated the effects of IL-12 on mechanical tooth movement in mice.DesignA Ni–Ti closed coil spring was inserted between the upper incisors and the upper left first molar in mice. IL-12 was injected locally adjacent to the first molar every other day during the experimental period, at doses varying from 0 to 1.5 μg/day. After 12 days, the animals were killed and their jaws were processed for histological evaluation using tartrate-resistant acid phosphatase (TRAP) and TdT-mediated dUTP-biotin nick end-labelling (TUNEL) staining, and measurements of the root resorption area.ResultsIn the IL-12-treated mice, tooth movement and root resorption appeared to be reduced. In TUNEL-stained sections, many apoptotic cells were recognized on the pressure side in the IL-12-treated mice.ConclusionsOur findings suggest that IL-12 inhibits not only mechanical tooth movement, but also root resorption during orthodontic tooth movement. These findings may arise through apoptosis induced by IL-12.     

Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease in acute ischemic stroke patients

Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R ² = 0.048, p < 0.001 and R ² = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.     

Respiratory dysfunction in patients severely affected by GNE myopathy (distal myopathy with rimmed vacuoles)

GNE myopathy is a rare and mildly progressive autosomal recessive myopathy caused by GNE mutations. Respiratory dysfunction has not been reported in GNE myopathy patients. In this study, we retrospectively reviewed the respiratory function of 39 severely affected GNE myopathy patients (13 men, 26 women) from medical records, and compared these parameters with various other patient characteristics (e.g., GNE mutations, age at onset, creatine kinase levels, and being wheelchair-bound) for correlations. The mean % forced vital capacity [FVC] was 92 (26) (range, 16–128). In 12/39 (31%) patients, %FVC was <80%. Of these 12 patients, 11 (92%) were entirely wheelchair-dependent. These patients exhibited significantly earlier onset (20 [4] vs. 30 [8] years, p < 0.001) and lower creatine kinase levels (56 [71] vs. 279 [185] IU/L) than patients with normal respiratory function. Two patients exhibited severe respiratory failure and required non-invasive positive pressure ventilation. Patients with a homozygous mutation in the N-acetylmannosamine kinase domain exhibited lower %FVC, while only one compound heterozygous patient with separate mutations in the uridinediphosphate-N-acetylglucosamine 2-epimerase and the N-acetylmannosamine kinase domains had respiratory dysfunction. Our results collectively suggest that GNE myopathy can cause severe respiratory failure. Respiratory dysfunction should be carefully monitored in patients with advanced GNE myopathy characterized by early onset and homozygous homozygous mutations in the N-acetylmannosamine kinase domain.     

Limb-girdle muscular dystrophy type 2I is not rare in Taiwan

Alpha-dystroglycanopathy is caused by the glycosylation defects of α-dystroglycan (α-DG). The clinical spectrum ranges from severe congenital muscular dystrophy (CMD) to later-onset limb girdle muscular dystrophy (LGMD). Among all α-dystroglycanopathies, LGMD type 2I caused by FKRP mutations is most commonly seen in Europe but appears to be rare in Asia. We screened uncategorized 40 LGMD and 10 CMD patients by immunohistochemistry for α-DG and found 7 with reduced α-DG immunostaining. Immunoblotting with laminin overlay assay confirmed the impaired glycosylation of α-DG. Among them, five LGMD patients harbored FKRP mutations leading to the diagnosis of LGMD2I. One common mutation, c.948delC, was identified and cardiomyopathy was found to be very common in our cohort. Muscle images showed severe involvement of gluteal muscles and posterior compartment at both thigh and calf levels, which is helpful for the differential diagnosis. Due to the higher frequency of LGMD2I with cardiomyopathy in our series, the early introduction of mutation analysis of FKRP in undiagnosed Taiwanese LGMD patients is highly recommended.     

Elevated urinary β2 microglobulin in the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy

Here we report what is to our knowledge the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy. The index case is a 52-year-old man with almost 40 years of progressive proximal muscle weakness. High urinary β2 microglobulin, normal serum β2 microglobulin, autophagic vacuoles with sarcolemmal features, and a hemizygous c.164–7T>G mutation in the VMA21 gene were found. His two maternal uncles had similar clinicopathological findings. High urinary β2 microglobulin without obvious renal dysfunction might result from decreased urine acidification in the distal convoluted tubules caused by the VMA21 gene mutation. These findings might prove to be useful as a preliminary marker suggestive of X-linked myopathy with excessive autophagy.