Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PURPOSE: To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. MATERIALS AND METHODS: Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were 'stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)'. These tests reported the centre of pressure data 'ellipse area, perimeter, front/back and mediolateral standard deviations'. RESULTS: There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward-backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). CONCLUSION: This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.

Adjacent Segment Disease (ASD) in Incidental Segmental Fused Vertebra and Comparison With the Effect of Stabilization Systems on ASD.

Objective Adjacent segment disease is a controversial process after spine stabilization. The two important factors discussed are natural aging and hypermobility in incidental segmental fusion anomalies; patients have two or more fused vertebrae from birth, which are the results of spinal movement restriction due to the fusion of some spinal units. This article's main purpose is to determine the degree of relationship of hypermobility and the aging process in the deterioration of the disks adjacent to fusion. Methods In this study, the degenerative process developed by hypermobility in the adjacent segment due to incidental segmental fusion was evaluated. The MRI images of 52 adjacent and nonadjacent disks of 45 patients in total were analyzed according to the Pfirrmann grading systems. The average Pfirrmann rating of the disks just above and below the fused segment and the distant first, second, and third non-neighboring levels were evaluated and calculated, respectively. Results The highest rate of incidental fusion is determined on the cervical area with 51.9%, followed by the thoracal area with 32.7%, and the lumbar area with 15.4%. Damage to the adjacent segment disks in cases with incidental fusion can still be seen at any age, with fusion, indicating that the hypermobility effect plays a more prominent role. The evidence of hypermobility without aging is that the segments adjacent to fusion undergo more degeneration than the distant disks. Conclusion Adjacent segment disease is under the influence of many factors. Our findings suggest that its incidence is increasing with the pathological processes initiated by hypermobility. It seems that, at least, it carries equal importance as compared to age. Fusion surgeries damage the adjacent segments under the influence of the passage of time beyond the physiological aging of the patient.

Clinical and radiological outcomes after correction of degenerative lumbar scoliosis with dynamic stabilization (with the help of a rigid rod); and describing an alternative technique.

Sharing clinical and radiological results in patients with degenerative lumbar scoliosis (DLS) treated surgically with dynamic system and describing an alternative technique for scoliosis correction. Between 2013 and 2018, 48 patients with flexible degenerative lumbar scoliosis (DLS) were operated with dynamic stabilization with Polyetheretherketone Rod (PEEK rod) after rigid rod application. Preoperative and postoperative scoliosis angles (standing and supine) were statistically compared. Preoperative and postoperative low back pain (LBP) Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were compared. In addition, preoperative C7 Sagittal Vertical Axis (SVA) values and lumbar lordosis angles were compared with postoperative values. The mean follow-up period of the patients was 48.3 months (range 30-76), the mean age was 67.08 (range 49-84). While the average Cobb angle of all patients was 9.65 in preoperative supine position, the average Cobb angle with standing position was 19.73. The mean standing Cobb angle of the patients after surgery was 3.52. The mean Cobb angle in the supine position after surgery was 3.02. The difference between the preoperative and postoperative patients' Cobb angles in standing and supine position were statistically significant (p:0,000, p:0,000, respectively). The differences of VAS and ODI scores between preoperative and postoperative period were statistically significantly (p:0,000, p:0,000; respectively). Especially in patients with flexible LDS, the technique we have defined and dynamic stabilization with PEEK rod provides significant correction. There was no loss of correction in our patients during postoperative follow-up period. PEEK rod is insufficient for lordosis increase and correction of SVA values.

Investigating the effects of subthalamic Nucleus-Deep brain stimulation on the voice quality.

Introduction: Deep brain stimulation (DBS) is a standard surgical treatment method which is generally applied to subthalamic nucleus in Parkinson's patients in cases where medical treatment is insufficient in treating the motor symptoms. It is known that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) treats many motor symptoms. However, the results of studies on speech and voice vary. The aim of the study is analysing the effect of STN-DBS on the characteristics of voice.Materials/methods: A total of 12 patients, (8 male-4 female) with an age average of 58.8 ± 9.6, who have been applied DBS surgery on STN included in the study. The voice recordings of the patients have been done prior to surgery and 6 months after the surgery. The evaluation of voice has been carried out through the instrumental method. The patients' voice recordings of the /a,e,i/ vowels have been done. The obtained recordings were evaluated by the Praat programme and the effects on jhitter, shimmer, fundamental frequency (F0) and noise harmonic rate (NHR) were analysed.Results: Numerical values of F0 of all female participants have been decreased for all of the vowels postoperatively. In the females; jhitter and fraction parameters were found to be significantly different (0.056 and 0.017, perspectively) for the vowel /e/. In addition, p values in the shimmer for vowels /e,i/ were thought to be clinically significant (.087, .079 and .076) respectively. All these changes in second measurements were found to indicate worsening vocal quality after the DBS in females. In males, there is not any significant difference observed between two measures in any of the parameters of any vowels.Conclusions: Acoustic voice quality deteriorated after STN-DBS predominantly for females however this deterioration was not prominent audio-perceptually. This finding commented as a result of the fact that that voice quality deviance of the participants was not severe.

Analysis of the effects of subthalamic nucleus deep brain stimulation on somatosensation in Parkinson's disease patients.

OBJECTIVE: Despite the subthalamic nucleus (STN) deep brain stimulation (DBS) is a treatment commonly used to ameliorate the motor symptoms of Parkinson's disease (PD), its effects on somatosensation is unclear. The purpose of this study was to investigate the potential effects of DBS on temperature, proprioceptive, tactile, exteroceptive, pain and cortical sensations, and odor identification in PD patients. METHODS: The study included 14 patients (with a mean age of 59.78 ± 11.03 years; range, 44-70 years) with idiopathic PD who underwent DBS surgery for movement disorders caused by PD at the same Neurosurgery Department. All patients were tested while DBS was turned on (DBS-ON) and off (DBS-OFF). To clearly observe the effect of removing stimulation off, DBS devices were turned off by experimental clinical personnel for a minimum duration of 30 min prior to examination. Temperature, proprioceptive, tactile, exteroceptive, pain and cortical sensations, and odor identification were examined. RESULTS: We found that two-point discrimination was significantly lower during DBS-ON than DBS-OFF (p = 0.031). Tactile sensation and kinesthesia deviation degree were lower during DBS-ON than DBS-OFF, but were non-significant (p > 0.05). The number of correct answers on an assessment of graphesthesia was higher during DBS-ON, but was non-significant as well (p > 0.05). Odor identification was better during DBS-OFF. CONCLUSIONS: DBS may have an effective role to improve somatosensation and DBS-related benefits may not be explained by improvements in motor function alone, but rather by enhanced somatosensory processing. Further studies with larger study groups are needed.

Complications of 2-Level Dynamic Stabilization: A Correlative Clinical and Radiological Analysis at Two-Year Follow-up on 103 Patients.

AIM: To investigate the postoperative complications, such as screw loosening, screw breakage and adjacent segment disease (ASD), in patients who underwent surgery with 2-level dynamic stabilization systems. MATERIAL AND METHODS: Postoperative complications, clinical improvements and radiological parameters in patients who underwent surgery using a dynamic system for 2-level lumbar stabilization were retrospectively reviewed. A total of 103 patients with lumbar degenerative spinal instability underwent 2-level dynamic stabilization. Clinical findings were reviewed at 2-year followup. Screw breakage and loosening were evaluated during this duration together with clinical findings. RESULTS: Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores were significantly decreased at the four-month evaluation, and they were also decreased at the 1-year follow up and at the 24th postoperative month. ASD was diagnosed in twelve (8 females, 4 males) of the 103 patients in the follow-up radiological and clinical controls. There were 9 screw breakages and 4 screw loosening cases. The complication rate of 2-level dynamic stabilization was high in this study. CONCLUSION: Our results showed that complications (screw loosening or breakage and adjacent segment disease) are not rare after 2-level dynamic stabilization, unlike the acceptable results with the single-level dynamic system. The most probable explanation is that the instrument system behaves more rigidly with every additional segment.

Investigating the effect of STN-DBS stimulation and different frequency settings on the acoustic-articulatory features of vowels.

INTRODUCTION: Parkinson's disease (PD) is the second most frequent progressive neuro-degenerative disorder. In addition to motor symptoms, nonmotor symptoms and voice and speech disorders can also develop in 90% of PD patients. The aim of our study was to investigate the effects of DBS and different DBS frequencies on speech acoustics of vowels in PD patients. METHODS: The study included 16 patients who underwent STN-DBS surgery due to PD. The voice recordings for the vowels including [a], [e], [i], and [o] were performed at frequencies including 230, 130, 90, and 60 Hz and off-stimulation. The voice recordings were gathered and evaluated by the Praat software, and the effects on the first (F1), second (F2), and third formant (F3) frequencies were analyzed. RESULTS: A significant difference was found for the F1 value of the vowel [a] at 130 Hz compared to off-stimulation. However, no significant difference was found between the three formant frequencies with regard to the stimulation frequencies and off-stimulation. In addition, though not statistically significant, stimulation at 60 and 230 Hz led to several differences in the formant frequencies of other three vowels. CONCLUSION: Our results indicated that STN-DBS stimulation at 130 Hz had a significant positive effect on articulation of [a] compared to off-stimulation. Although there is not any statistical significant stimulation at 60 and 230 Hz may also have an effect on the articulation of [e], [i], and [o] but this effect needs to be investigated in future studies with higher numbers of participants.

Influences of Ivabradine treatment on serum levels of cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in patients with chronic heart failure.

Chronic heart failure (CHF) represents a major cause of hospitalization and death. Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients. In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current If), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena. Patients were divided into three groups based on the etiology of CHF: dilated cardiomyopathy (DCM, n=20), ischemic cardiomyopathy (ICM, n=20) and hypertensive cardiomyopathy (HCM, n=10). The patients were administered Ivabradine (5 mg, bid for 3 months, and 7.5 mg bid for further 3 months). Analyses of cardiovascular biomarkers were performed at baseline as well as at 3- and 6-month follow-ups. At 6-month follow-up, GDF-15 levels were significantly reduced compared to baseline levels (P=0.0215), indicating a reduction in the progress of cardiac remodeling. H-FABP concentration was significantly lower in DCM patients compared to ICM (1.89 vs 3.24 µg/mL) and HCM patients (1.89 vs 3.80 µg/mL), and decreased over the 6-month follow-up (P=0.0151). suPAR median levels remained elevated, implying major ongoing inflammatory processes. As shown by significant decreases in GDF-15 and H-FABP levels, a reduction in ventricular remodeling and sub-clinical ischemia could be assumed. However, markers of hemodynamic stress (sST2) and inflammation (suPAR) showed no change or progression after 6 months of Ivabradine treatment in CHF patients. Further studies are necessary to validate the clinical applicability of these novel cardiovascular biomarkers.

Percutaneous Kyphoplasty: Is Bilateral Approach Necessary?

STUDY DESIGN: A multicenter retrospective study of patients who underwent unilateral and bilateral balloon kyphoplasty. OBJECTIVE: The aim of this study was to compare the radiographic and clinical results of unilateral and bilateral balloon kyphoplasty to treat osteoporotic vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Percutaneous kyphoplasty has long been used as a successful method in the treatment of osteoporotic vertebral compression fractures. Although the bilateral approach is considered to be the mainstay application of percutaneous kyphoplasty, the unilateral approach has also been shown to be sufficient and even more effective in some cases. METHODS: A total of 87 patients who underwent percutaneous kyphoplasty due to osteoporotic vertebral compression fractures between 2009 and 2016 were retrospectively evaluated and divided into two groups as patients who underwent unilateral or bilateral percutaneous kyphoplasty. Unilateral percutaneous kyphoplasty was performed in 36 and bilateral percutaneous kyphoplasty in 51 patients. The groups were compared in terms of clinical outcomes, radiological findings, and complications. Clinical outcomes were evaluated using Visual Analogue Scale and Oswestry Disability Index and the radiological findings were evaluated by comparing the preoperative and postoperative day 1 and year 1 values of anterior, middle, and posterior vertebral heights and kyphosis angle. RESULTS: Clinical improvement occurred in both groups but no significant difference was observed. In radiological workup, no significant difference was found between the groups in terms of improvements in vertebral heights and kyphosis angle. Operative time and the amount of cement used for the surgery were significantly lower in the patients that underwent unilateral kyphoplasty. CONCLUSION: Unilateral percutaneous kyphoplasty is as effective as bilateral percutaneous kyphoplasty both radiologically and clinically. Operative time and the amount of cement used for the surgery are significantly lower in unilateral kyphoplasty, which may play a role in decreasing complication rates. LEVEL OF EVIDENCE: 3.

Use of programmable versus nonprogrammable shunts in the management of normal pressure hydrocephalus: A multicenter retrospective study with cost-benefit analysis in Turkey.

Ventriculoperitoneal shunt systems that are used in the treatment of normal pressure hydrocephalus are often associated with drainage problems. Adjustable shunt systems can prevent or treat these problems, but they may be expensive. The aim of our study is to compare the complications and total cost of several shunt systems.Patients with normal pressure hydrocephalus who underwent ventriculoperitoneal shunting between 2011 and 2016 were included in the study. The study involves patient consent and the informed consent was given. Complications and the average cost per person were compared between patients with adjustable and nonadjustable shunts. Shunt prices, surgical complications, and revision costs were taken into account to calculate the average cost.Of the 110 patients who were evaluated, 80 had a nonadjustable shunt and 30 had an adjustable shunt. In the group with adjustable shunts, the rates of subdural effusion and hematoma were 19.73% and 3.29%, respectively. In the group with nonadjustable shunts, these rates were 22.75% and 13.75%, respectively. One patient in the adjustable group underwent surgery for subdural hematoma, while 8 patients in the nonadjustable group underwent the same surgery. Ten patients required surgical intervention for subdural effusion and existing shunt systems in these patients were replaced by an adjustable shunt system. When these additional costs were factored into the analysis, the difference in cost between the shunt systems was reduced from 600 United States dollars (USD) to 111 USD.When the complications and additional costs that arise during surgical treatment of normal pressure hydrocephalus were considered, the price difference between adjustable and nonadjustable shunt systems was estimated to be much lower.

Lumbar Single-Level Dynamic Stabilization with Semi-Rigid and Full Dynamic Systems: A Retrospective Clinical and Radiological Analysis of 71 Patients.

BACKGROUND: This study compares the clinical and radiological results of three most commonly used dynamic stabilization systems in the field of orthopedic surgery. METHODS: A total of 71 patients underwent single-level posterior transpedicular dynamic stabilization between 2011 and 2014 due to lumbar degenerative disc disease. Three different dynamic systems used include: (1) the Dynesys system; (2) a dynamic screw with a PEEK rod; and (3) a full dynamic system (a dynamic screw with a dynamic rod; BalanC). The mean patient age was 45.8 years. The mean follow-up was 29.7 months. Clinical and radiological data were obtained for each patient preoperatively and at 6, 12, and 24 months of follow-up. RESULTS: Clinical outcomes were significantly improved in all patients. There were no significant differences in the radiological outcomes among the groups divided according to the system used. Screw loosening was detected in 2 patients, and 1 patient developed screw breakage. All patients with screw loosening or breakage underwent revision surgery. CONCLUSIONS: Each procedure offered satisfactory outcome regardless of which system was applied.

Disc Rehydration after Dynamic Stabilization: A Report of 59 Cases.

STUDY DESIGN: A retrospective study investigating decrease in the nucleus pulposus signal intensity or disc height on magnetic resonance imaging (MRI) and disc degeneration. PURPOSE: Although a degenerated disc cannot self-regenerate, distraction or stabilization may provide suitable conditions for rehydration and possible regeneration. This study aimed to evaluate clinical outcomes and disc regeneration via MRI in a series of patients with degenerative disc disease (DDD) who underwent lumbar stabilization with a dynamic stabilization system (DSS). OVERVIEW OF LITERATURE: A dynamic system provides rehydration during early DDD. METHODS: Fifty-nine patients (mean age, 46.5 years) who undedwent stabilization with DSS for segmental instability (painful black disc) between 2004 and 2014 were retrospectively evaluated. All patients underwent MRI preoperatively and 12 months postoperatively. Intervertebral disc (IVD) degeneration grades at the implanted segment were categorized using the Pfirrmann classification system. Patients were followed for a mean of 6.4 years, and clinical outcomes were based on visual analog scale (VAS) and Oswestry disability index (ODI) scores. RESULTS: Significant improvements in back pain VAS and ODI scores from before surgery (7 and 68%, respectively) were reported at 6 (2.85 and 27.4%, respectively) and 12 months postoperatively (1.8 and 16.3%, respectively). Postoperative IVD changes were observed in 28 patients. Improvement was observed in 20 patients (34%), whereas progressive degeneration was observed in eight patients (13.5%). Thirty-one patients (52.5%) exhibited neither improvement nor progression. Single Pfirrmann grade improvements were observed in 29% of the patients and two-grade improvements were observed in 5%. CONCLUSIONS: Our observations support the theory that physiological movement and a balanced load distribution are necessary for disc regeneration. We conclude that DSS may decelerate the degeneration process and appears to facilitate regeneration.

A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure.

BACKGROUND: Heart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM). MATERIALS AND METHODS: A total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA. RESULTS: Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p<0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p<0.0001, GDF-15 p=0.0394, suPAR p=0.0029, H-FABP p<0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p<0.0001) and diabetes (sST2 p=0.0021, GDF-15 p=0.0055, suPAR p=0.0339, H-FABP p=0.0010) were significantly associated with a rise in cardiac biomarkers. CONCLUSION: Novel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.

Infected colloid cyst.

INTRODUCTION: Colloid cysts are the most common pathologic lesions of the third ventricle. Although they are histologically benign, they may grow and can cause the hydrocephalus. A 5-year-old male patient underwent to surgery with the diagnosis of colloid cyst. In operation, after the anterior transcallosal approach, the cyst was punctured by syringe and obviously pus aspirated. CONCLUSION: Colloid cysts mostly remain silent and detected incidentally. Although it is rarely defined, rhinorrhea, hypopituitarism, diabetes insipidus, spasmodic torticollis, drop attack, aseptic meningitis, and coexistence with neurocysticercosis have been reported, but this is the first reported case of an infected colloid cyst.

Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage.

BACKGROUND: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. OBJECTIVE: So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. METHOD: Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. RESULTS: During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± 1.89 pg/ml in the survival group. Furthermore, it was 10.22 ± 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.01 for all). CONCLUSION: The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management.

A Very Rare Complication of Cerebral Hydatid Cyst Surgery: Cortical Collapse.

Hydatid diseases are still endemic pathologies in developing countries which generally needs surgical treatment. The main aim of the treatment is total cyst evacuation without rupture. Dowling technique is preferable for this aim. There are various complications of hydatid disease surgery which include cortical collapse which is very serious and can be mortal. Our case was a 6-year-old boy diagnosed with a solitary isointense cystic mass in the left parietal region. There was no surrounding edema. The cyst was completely evacuated with Dowling technique without rupture. In about 10 min after evacuation, hemispheric cortical collapse occurred, and the patient developed cardiac arrest. Although cortical collapse is a rare complication, it can cause perioperative mortality. Special care and efforts should be taken as not to form large defects after cyst evacuation to prevent cortical collapse and related mortality.

Decrease in circulating plasmacytoid dendritic cells during short-term systemic normobaric hypoxia.

BACKGROUND: During exposure to high altitude, the immune system is altered. During hypoxia, an increase in interleukin (IL)-6 and high sensitivity C-reactive protein (hs-CRP), and an increase in natural killer cells and decrease in T cells in blood was shown. However, the impact of hypoxia on dendritic cells has not been investigated yet. MATERIAL AND METHODS: Twelve healthy volunteers were subjected to a transient normobaric hypoxia for 6·5 h simulating an oxygen concentration at 5500 m. During exposure to hypoxia, blood samples were collected and analysed by flow cytometrical cell sorting (FACS) for circulating myeloid (mDCs) and plasmacytoid (pDCs) DCs. Serum levels of IL-6 and tumour necrosis factor (TNF)-α were analysed. In a cell culture hypoxia chamber, blood samples were subjected to the same hypoxia and analysed regarding DCs. RESULTS: Exposure to normobaric hypoxia induced a significant decrease in circulating pDCs about 45% (P = 0·001) but not of mDC compared to baseline normoxia. Furthermore, we observed a significant increase of TNF-α about 340% (P = 0·03) and of IL-6 about 286% (P = 0·002). In cell culture experiments exposure of blood to hypoxia led to no significant changes in DCs, so that a direct cytotoxic effect was excluded. During hypoxia, we observed a transient increase in stromal-derived factor 1 (SDF-1) which is important for pDC tissue recruitment. CONCLUSIONS: We show a significant decrease in circulating pDCs during hypoxia in parallel to a pro-inflammatory response. Further studies are necessary to evaluate whether the decrease in circulating pDCs might be the result of an enhanced tissue recruitment.

Decrease in circulating dendritic cell precursors in patients with peripheral artery disease.

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. Inflammation is important for initiation and progression of the disease. Dendritic cells (DCs) as antigen-presenting cells play an important role in the immune system. Therefore, we hypothesize that, in patients with PAD, DCPs might be reduced in blood due to their recruitment into the vascular wall and induce a proinflammatory response. The numbers of myeloid DCPs, plasmacytoid DCPs, and total DCPs were analyzed by flow cytometry in blood of patients with PAD (n = 52) compared to controls (n = 60). Femoralis plaques (n = 12) of patients who underwent surgery were immunostained for CD209 and CD83 (mDCs) as well as CD304, CD123 (pDCs), and HLA-DR. In patients with PAD, a significant decrease in mDCPs, pDCPs, and tDCPs was observed. In immunostaining, markers indicative for mDCs (CD209: 16 versus 8 cells/0.1 mm(2), P = 0.02; CD83: 19 versus 5 cells/0.1 mm(2), P = 0.03) were significantly elevated in femoralis plaques compared to control vessels. We show for the first time that mDCPs, pDCPs, and tDCPs are significantly reduced in patients with PAD. Immunohistochemical analysis unraveled that the decrease in DCPs might be due to their recruitment into atherosclerotic plaques.

Circulating dendritic cell precursors in chronic kidney disease: a cross-sectional study.

BACKGROUND: Dendritic cells (DC) are professional antigen-presenting cells in the immune system. They patrol the blood as circulating dendritic cell precursors (DCP). Decreased blood DCP count has been shown to be related to atherosclerotic plaque burden. Since chronic kidney disease (CKD) is associated with chronic inflammation and increased cardiovascular risk, the aim of our study was to investigate a potential effect of CKD on circulating DCP numbers especially in patients with a history of cardiovascular disease. METHODS: The number of circulating myeloid (mDCP), plasmacytoid (pDCP), and total DCP (tDCP) was analysed by flow cytometry in 245 patients with CKD stage 3 (with and without known cardiovascular events) and 85 coronary healthy controls. In addition, data were compared with a historical group of 130 patients with known coronary artery disease (CAD). RESULTS: Compared to controls, patients with CKD 3 revealed a significant decrease in circulating mDCP (-29%), pDCP (-43%), and tDCP (-38%) (P < 0.001, respectively). Compared with CAD-patients, the decrease in circulating DCP in CKD was comparable or even more pronounced indicating a potential role for DCP in cardiovascular risk potentiation due to CKD. CONCLUSIONS: Based on previous findings in CAD, the marked decrease of DCP in CKD implicates a potential role for DCP as a mediator of cardiovascular disease. Whether DCP in CKD may act as new cardiovascular biomarkers needs to be established in future prospective trials.

Decrease in dendritic cells in endomyocardial biopsies of human dilated cardiomyopathy.

AIMS: Dendritic cells (DCs) are sentinels of the immune system-their role in myocardial disease is unknown as yet. We investigated their myocardial presence in human dilated cardiomyopathy (DCM). METHODS AND RESULTS: Endomyocardial biopsies from 72 patients with DCM (EF ∼30%), as well as myocardial specimens from 18 suicide or accident victims were immunohistochemically analysed for myeloid and plasmacytoid DCs, antigen-presenting cells (APCs), and other leucocytes; also tissue fibrosis and apoptosis were histologically quantified. The myocardial viral genome was identified through polymerase chain reaction, and patients underwent clinical follow-up in 3-6 months. We found myocardial DCs of all examined subtypes and maturation stages (fascin, CD11c, CD209, CD83, and CD304), as well as markers for APCs (HLA-DR and CD40) and T-cell activation (CD69) to be significantly decreased in DCM compared with controls. In contrast, regulatory T cells (the GITR epitope), apoptosis (by TUNEL reaction and immunostaining with BCL-2), and a DC chemokine receptor (CCR7) were overexpressed, while no significant differences were observed for macrophages (CD68). Immature myeloid and plasmacytoid DCs strongly correlated with endothelial progenitor cells (CD34), which were similarly reduced in DCM, and inversely correlated with fibrosis. Myeloid DCs were especially reduced in virus-positive biopsies, and their numbers correlated with positive change in EF (ΔEF) at follow-up. CONCLUSION: Myocardial DCs are reduced in heart biopsies of symptomatic DCM patients. Such a reduction correlates with an unfavourable short-term outcome in terms of EF, and could result from myocardial tissue damage, cellular death, and insufficient vascularization in chronic heart failure.