Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats

BACKGROUND: Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury. METHODS: Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation. RESULTS: All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each). CONCLUSIONS: In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.     

Laparoscopic anatrophic nephrolithotomy

Management of staghorn calculi is still a challenge. To combine the surgical principles of treatment with the minimal invasive access we performed a laparoscopic anatrophic nephrolithotomy in a female patient successfully. Patient was discharged free of stone on fifth postoperative day. No complications occurred.     

A numerical simulation of intranasal air temperature during inspiration

OBJECTIVES/HYPOTHESIS: In vivo measurements of the intranasal air temperature are feasible. The present study was designed to reproduce temperature distributions within the human nasal cavity by means of numerical simulation. STUDY DESIGN: Numerical simulation. METHODS: Based on computed tomography (CT), a steady-state computational fluid dynamics (CFD) simulation was performed displaying the temperature distribution throughout the human nasal cavity during inspiration. The results of the numerical simulation were compared with in vivo temperature measurements. RESULTS: The numerical simulation demonstrated that the major increase of the inspiratory air temperature can be found in the anterior nasal segment, especially within the nasal valve area, which is comparable to in vivo measurements. Intranasal areas of high temperature were characterized by turbulent airflow with vortices of low velocity. The results of numerical simulation showed an excellent comparability to the results of previous in vivo measurements in the entire nasal cavity. CONCLUSION: The anterior nasal segment is the most effective part of the nose in heating of the ambient air. The findings demonstrated the complexity of the relationship between airflow patterns and heating of inspired air. A numerical simulation of the temperature distribution using CFD is practicable.     

C2 monitoring in maintenance renal transplant recipients: is it worthwhile?

Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2 and CsA trough concentration (C0) measurements were performed in 1032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L], CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1, and S-creatinine=141+/-58 mumol/L). A univariate analysis of variance showed that patients with C2 levels between 700 and 800 mug/L (n=203, S-creatinine=136+/-49 mumol/L) had significantly lower S-creatinine levels compared with patients with C2 levels greater than 950 mug/L (n=94, S-creatinine=152+/-56 mumol/L) (P<0.02). The same was true for patients with C2 levels less than 450 mug/L (n=95, S-creatinine 141+/-72 mumol/L) (P<0.05) when compared with patients with C2 levels greater than 950 mug/L. There was no significant difference in S-creatinine between patients in the low and intermediate C2 group; 666 patients had C0 levels in the therapeutic range (75-125 mumol/L). A linear regression showed a significant relation between S-creatinine and C2 for these patients (P=0.03). The corresponding relation between S-creatinine and C0 was nonsignificant (P=0.3). Monitoring of C2 in maintenance patients is a valuable tool to detect overexposure to CsA. Until results from prospective studies are available, we recommend C0 in the therapeutic range and reduction in CsA in overexposed patients, aiming at a C2 value between 700 and 800 mug/L.     

Influence of very low dietary intake of marine oil on some functional aspects of immune cells in healthy elderly people

Ageing is a multifactorial process involving decreased antioxidant defences and immune functions. n-3 Polyunsaturated fatty acids have been associated with human health benefits, especially against inflammatory and autoimmune diseases. However, their immunomodulatory effects were usually observed with high dosages (>2 g/d) known to increase lipid peroxidation. In contrast, very low doses, that may prevent lipid peroxidation, might affect the immune system differently. To study the latter hypothesis further, we investigated whether the supplementation of healthy elderly people with very low doses of marine oil (MO), a docosahexaenoate (DHA)- and eicosapentaenoate (EPA)-rich triacylglycerol, was able to affect lymphocyte proliferation and biochemical markers known to be altered with age. In a randomized, double-blind design, twenty healthy elderly subjects were assigned to a placebo group (600 mg sunflower oil/d) or to a group consuming 600 mg MO/d providing 150 mg DHA + 30 mg (EPA) for 6 weeks. At day 42, the proliferative responses of lymphocytes to several mitogens were significantly (P<0.01) decreased in the MO group compared with control values. This was accompanied by a slight lowering of their cytosolic cyclic nucleotide phosphodiesterase (PDE) activity, a marked and significant (P<0.05) increase of their particulate PDE activity (+56-57 %) and a slight but significant (P<0.05) increase in cyclic nucleotide intracellular levels. At the same time, the glutathione peroxidase activity was markedly and significantly (P<0.01) depressed in the MO group. None of these modifications could be seen in the placebo group. Collectively, these results demonstrate that even very low doses of n-3 fatty acids are sufficient to affect the immune responses of elderly subjects.     

Comparison of histomorphometric and radiographic effects of growth guidance with tension-band devices (eight-Plate and FlexTack) in a pig model

Background and purpose — Temporary hemiepiphysiodesis for growth modulation in skeletally immature patients is a long-known technique. Recently the use of tension-band devices has become popular. This study compares 2 tension-band implants (eight-Plate and FlexTack) regarding their effects on the growth plate.Animals and methods — 12 pigs in 2 equally sized groups (A and B) were investigated. The right proximal medial tibia was treated with either eight-Plate or FlexTack. The left tibia of the same pig was treated with the opposite implant. After 9 weeks all implants were removed. Animals in group B were then hosted for another 5 weeks. Histomorphometric analysis of the growth plate was carried out after 9 and 14 weeks, respectively. Radiographs were taken at implantation, removal, and after 14 weeks.Results — Both tension-band devices achieved a statistically significant and clinically relevant growth inhibition, whereas the effect appeared to be more distinct after the use of FlexTack. Implant-related complications or physeal damage was not observed. After implant removal, rebound phenomenon was radiologically observed in all cases. The growth plates treated with eight-Plate showed a paradox reversal of the zonal distributions, with an increase of the proliferative zones at the previously arrested medial aspect of the physis and a decrease laterally.Interpretation — Both eight-Plate and FlexTack proved to be appropriate devices for growth-guiding treatment. The radiographic evaluation showed a change in angular axes after treatment with each implant, while the correction appeared to be faster with FlexTack. The paradox cartilaginous reaction observed after removal of the eight-Plate might be a histopathological correlate for rebound phenomenon.

To achieve realignment of angular deformities in skeletally immature patients, remaining bone growth can be used for growth modulation procedures to avoid extensive surgical interventions (Stevens 2007). Temporary hemiepiphysiodesis (THE) aims to mechanically inhibit growth on one side of the physis through a bridging implant. The procedure has to be performed before skeletal maturity, to maintain sufficient potential for correction while also reducing the risk of relapse of the deformity after implant removal (rebound phenomenon). Blount in 1949 described a stapling technique for THE, which provided good results in the correction of angular deformities but was later linked to complications like implant failure and physeal damage (Blount and Clarke 1949, Kanellopoulos et al. 2011, Stevens 2007). In 2007 Stevens introduced a non-locking 2-hole plate (eight-Plate [EP], Orthofix Medical Inc, Lewisville, TX, USA) based on the tension-band principle (Stevens 2007). Even though treatment with the EP seems to have an overall decreased complication rate, screw breakage is still reported rather frequently (Schroerlucke et al. 2009, Burghardt et al. 2010, 2011, Scott 2012, Vogt et al. 2016). This led to the development of a flexible staple (FlexTack [FT], Merete GmbH, Berlin, Germany). Both implants, EP and FT, achieve a tension-band effect through an extra-physeally located fulcrum of correction supposedly leading to reduced compression on the physis, thus decreasing the risk of premature closure of the physis (Vogt et al. 2016). Different from the EP, the FT is a 1-piece implant with a flexible mid-zone that provides dynamic bending under bone growth force.We examined the physeal response to THE with these 2 tension-band devices and whether there is a histomorphological correlate for the extent of the blockage between FT and EP. Additionally, we sought a possible histomorphological explanation for the excessive unilateral bone growth frequently occurring after implant removal, which might be linked to the incidence of rebound phenomenon.     

Skeletal distribution and biochemical parameters of Paget's disease

Quantitative bone scans were performed with 99mTc-EHDP in 170 untreated pagetic patients (93 men, 77 women; mean age, 65.4 years). The distribution of 863 pagetic skeletal locations was analyzed. Bone scans demonstrated 8.3% more pagetic sites than roentgenograms. The extent of Paget's disease was evaluated in each patient by a scintigraphic skeletal index. This index correlated with serum alkaline phosphatase (SAP) and urinary hydroxyproline (HyPro) levels, and also with hypocalcemic acute response to calcitonin. The correlation of SAP with an index of activity (extent index adjusted by uptake ratios) was better than with the nonadjusted index. Only 30.6% of pagetic sites were responsible for clinical symptoms. No correlation was found between age and skeletal index of the disease.     

Serum bone GLA-protein is not a sensitive marker of bone turnover in Paget's disease of bone

Summary Serum bone Gla-protein (sBGP) was measured in 32 patients with untreated Paget's disease of bone. Despite clinical and biological symptoms of active disease in all patients, sBGP was normal in 13/32 patients (41%). There was a striking discrepancy between the moderate increase of sBGP above normal values (11.4±4.5 vs 6.0±2.1 ng/ml) and the marked increase of both serum alkaline phosphatase (sAP) and urinary hydroxyproline (uOHP). sBGP was weakly correlated with sAP (r=0.50, p<0.01), uOHP (r=0.48, p<0.01) and with the extension of the disease (r=0.48, p<0.01), We conclude that sBGP is not a sensitive marker of bone turnover in patients with Paget's disease of bone, and should be interpreted with caution in this condition.     

Decreased cyclic nucleotide phosphodiesterase activity in human peripheral blood mononuclear cells from elderly women

1. Both adenosine 3':5'-cyclic monophosphate and guanosine 3':5'-cyclic monophosphate phosphodiesterase activities of peripheral blood mononuclear cells were markedly decreased in elderly women as compared with young control women. 2. In contrast, the ability of these cells to bind guanosine 5'-[beta, gamma-imido]triphosphate, a non-hydrolysable analogue of guanosine 5'-triphosphate, was the same in both groups. 3. These findings are discussed in the context of the decline in immune function which occurs with increasing age.