Showing papers by "Istanbul University published in 2009"

Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document.

Abstract: Abbreviations ACE: angiotensin-converting enzyme; BP: blood pressure; DBP: diastolic blood pressure; eGFR: estimated glomerular filtration rate; ESC: European Society of Cardiology; ESH: European Society of Hypertension; ET: endothelin; IMT: carotid intima-media thickness; JNC: Joint National Commit

EULAR Recommendations for the management of primary small and medium vessel vasculitis

Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Strict blood-pressure control and progression of renal failure in children.

Abstract: Background Although inhibition of the renin–angiotensin system delays the progression of renal failure in adults with chronic kidney disease, the blood-pressure target for optimal renal protection is controversial. We assessed the long-term renoprotective effect of intensified blood-pressure control among children who were receiving a fixed high dose of an angiotensin-converting–enzyme (ACE) inhibitor. Methods After a 6-month run-in period, 385 children, 3 to 18 years of age, with chronic kidney disease (glomerular filtration rate of 15 to 80 ml per minute per 1.73 m 2 of body-surface area) received ramipril at a dose of 6 mg per square meter of bodysurface area per day. Patients were randomly assigned to intensified blood-pressure control (with a target 24-hour mean arterial pressure below the 50th percentile) or conventional blood-pressure control (mean arterial pressure in the 50th to 95th percentile), achieved by the addition of antihypertensive therapy that does not target the renin–angiotensin system; patients were followed for 5 years. The primary end point was the time to a decline of 50% in the glomerular filtration rate or progression to end-stage renal disease. Secondary end points included changes in blood pressure, glomerular filtration rate, and urinary protein excretion. Results A total of 29.9% of the patients in the group that received intensified blood-pressure control reached the primary end point, as assessed by means of a Kaplan– Meier analysis, as compared with 41.7% in the group that received conventional blood-pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P = 0.02). The two groups did not differ significantly with respect to the type or incidence of adverse events or the cumulative rates of withdrawal from the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50% decrease, despite persistently good blood-pressure control. Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease. Conclusions Intensified blood-pressure control, with target 24-hour blood-pressure levels in the low range of normal, confers a substantial benefit with respect to renal function among children with chronic kidney disease. Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition. (ClinicalTrials.gov number, NCT00221845.)

The genomic basis of trophic strategy in marine bacteria.

Abstract: Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis RB2256, that serve as useful model organisms for copiotrophic and oligotrophic modes of life and specifically relate the genomic features to trophic strategy for these organisms and define their molecular mechanisms of adaptation. We developed a model for predicting trophic lifestyle from genome sequence data and tested >400,000 proteins representing >500 million nucleotides of sequence data from 126 genome sequences with metagenome data of whole environmental samples. When applied to available oceanic metagenome data (e.g., the Global Ocean Survey data) the model demonstrated that oligotrophs, and not the more readily isolatable copiotrophs, dominate the ocean's free-living microbial populations. Using our model, it is now possible to define the types of bacteria that specific ocean niches are capable of sustaining.

A genome-wide linkage and association scan reveals novel loci for autism

Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

EULAR recommendations for the management of large vessel vasculitis

Abstract: Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

Risk factors for hip fracture in European women: the MEDOS Study. Mediterranean Osteoporosis Study.

Abstract: The aims of this study were to determine common international risk factors for hip fracture in women aged 50 years or more. We studied women aged 50 years or more who sustained a hip fracture in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey over a 1-year period. Women aged 50 years or more selected from the neighborhood or population registers served as controls. Cases and controls were interviewed using a structured questionnaire on work, physical activity, exposure to sunlight, reproductive, history and gynecologic status, height, weight, mental score, and consumption of tobacco, alcohol, calcium, coffee, and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), short fertile period, low physical activity. lack of sunlight exposure, low milk consumption, no consumption of tea, and a poor mental score. No significant adverse effects of coffee or smoking were observed. Moderate intake of spirits was a protective factor in young adulthood, but otherwise no significant effect of alcohol intake was observed. For some risks, a threshold effect was observed. A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Thus, about half of the hip fractures could be explained on the basis of the potentially reversible risk factors sought. In contrast, the use of risk factors to "predict" hip fractures had moderate sensitivity and specificity. We conclude that variations in lifestyle factors are associated with significant differences in the risk of hip fracture, account for a large component of the total risk, and may be of some value in selecting individuals at high risk.

Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome

Abstract: Background The genetic etiologies of the hyper-IgE syndromes are diverse. Approximately 60% to 70% of patients with hyper-IgE syndrome have dominant mutations in STAT3, and a single patient was reported to have a homozygous TYK2 mutation. In the remaining patients with hyper-IgE syndrome, the genetic etiology has not yet been identified. Objectives We aimed to identify a gene that is mutated or deleted in autosomal recessive hyper-IgE syndrome. Methods We performed genome-wide single nucleotide polymorphism analysis for 9 patients with autosomal-recessive hyper-IgE syndrome to locate copy number variations and homozygous haplotypes. Homozygosity mapping was performed with 12 patients from 7 additional families. The candidate gene was analyzed by genomic and cDNA sequencing to identify causative alleles in a total of 27 patients with autosomal-recessive hyper-IgE syndrome. Results Subtelomeric biallelic microdeletions were identified in 5 patients at the terminus of chromosome 9p. In all 5 patients, the deleted interval involved dedicator of cytokinesis 8 (DOCK8) , encoding a protein implicated in the regulation of the actin cytoskeleton. Sequencing of patients without large deletions revealed 16 patients from 9 unrelated families with distinct homozygous mutations in DOCK8 causing premature termination, frameshift, splice site disruption, and single exon deletions and microdeletions. DOCK8 deficiency was associated with impaired activation of CD4 + and CD8 + T cells. Conclusion Autosomal-recessive mutations in DOCK8 are responsible for many, although not all, cases of autosomal-recessive hyper-IgE syndrome. DOCK8 disruption is associated with a phenotype of severe cellular immunodeficiency characterized by susceptibility to viral infections, atopic eczema, defective T-cell activation and T h 17 cell differentiation, and impaired eosinophil homeostasis and dysregulation of IgE.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative

Abstract: Objectives: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. Methods: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. Conclusions: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Fungal rhinosinusitis: A categorization and definitional schema addressing current controversies

Abstract: Background Fungal (rhino-) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies.

Abstract: Phosphotidylinositol (PtdIns) signaling is tightly regulated both spatially and temporally by subcellularly localized PtdIns kinases and phosphatases that dynamically alter downstream signaling events. Joubert syndrome is characterized by a specific midbrain-hindbrain malformation ('molar tooth sign'), variably associated retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly and is included in the newly emerging group of 'ciliopathies'. In individuals with Joubert disease genetically linked to JBTS1, we identified mutations in the INPP5E gene, encoding inositol polyphosphate-5-phosphatase E, which hydrolyzes the 5-phosphate of PtdIns(3,4,5)P3 and PtdIns(4,5)P2. Mutations clustered in the phosphatase domain and impaired 5-phosphatase activity, resulting in altered cellular PtdIns ratios. INPP5E localized to cilia in major organs affected by Joubert syndrome, and mutations promoted premature destabilization of cilia in response to stimulation. These data link PtdIns signaling to the primary cilium, a cellular structure that is becoming increasingly recognized for its role in mediating cell signals and neuronal function.

European Consensus Table On the Use of Botulinum Toxin Type a in Adult Spasticity

Abstract: A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current published data, which was collated following extensive literature searches, their assessment for level of evidence and discussion among the whole group. Published information is supplemented by expert opinion based on clinical experience from 16 European countries, involving 28 clinicians, who treat an average of approximately 200 patients annually, representing many thousand spasticity treatments with botulinum toxin per year.

Check-list of Additional Taxa to the Supplement Flora of Turkey IV

Abstract: The fourth check-list of the series entitled 'Additional taxa to the Flora of Turkey' comprises a total of 175 taxa based on data given in 162 papers published up until the end of 2007. It provides details of taxa not recorded in the 11 volumes of the Flora of Turkey and the East Aegean Islands nor in the there previously published supplementary check-lists.

Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers

Abstract: There are other benefits of vitamin D than those for bone health. To determine the association of serum 25-hydroxy vitamin D (25(OH)D) concentrations in newborns with acute lower respiratory infection (ALRI) and without clinical signs of rickets, and their mothers. The design comprises a hospital-based case-control study. The study group consisted of 25 newborns with ALRI who were admitted to neonatal intensive care unit and their mothers. Controls were 15 healthy newborns of the same age as the study group and their mothers. A commercial radioimmunoassay was used to measure 25(OH)D concentrations in serum for assessing vitamin D status. The two groups were similar in gestational week, birth weight, birth height, head circumference, age and gender. The mean serum 25(OH)D concentrations in the study group newborns were lower than those of the control group (9.12±8.88ng/ml and 16.33±13.42 ng/ml, respectively) (P=0.011). Also, mean serum 25(OH)D concentrations in the mothers of the study group were lower than those in the mothers of the control group (13.38±16.81 ng/ml and 22.79±16.93 ng/ml respectively) (P=0.012). In 87.5% of all newborns and 67.5% of all mothers, serum 25(OH)D concentrations were lower than 20 ng/ml. The 25(OH)D concentrations of newborns were highly correlated with mothers' serum 25(OH)D concentrations. Our findings suggest that newborns with subclinical vitamin D deficiency may have an increased risk of suffering from ALRI. The strong positive correlation between newborns' and mothers' 25(OH)D concentrations shows that adequate vitamin D supplementation of mothers should be emphasized during pregnancy especially in winter months.

Multifaceted Determinants for Achieving Glycemic Control: The International Diabetes Management Practice Study (IDMPS)

Abstract: OBJECTIVE—The International Diabetes Mellitus Practice Study is a 5-year survey documenting changes in diabetes treatment practice in developing regions. RESEARCH DESIGN AND METHODS—Logistic regression analysis was used to identify factors for achieving A1C <7% in 11,799 patients (1,898 type 1 diabetic and 9,901 type 2 diabetic) recruited by 937 physicians from 17 countries in Eastern Europe (n = 3,519), Asia (n = 5,888), Latin America (n = 2,116), and Africa (n = 276). RESULTS—Twenty-two percent of type 1 diabetic and 36% of type 2 diabetic patients never had A1C measurements. In those with values for A1C, blood pressure, and LDL cholesterol, 7.5% of type 1 diabetic (n = 696) and 3.6% of type 2 diabetic (n = 3,896) patients attained all three recommended targets (blood pressure <130/80 mmHg, LDL cholesterol <100 mg/dl, and A1C <7%). Self-monitoring of blood glucose was the only predictor for achieving the A1C goal in type 1 diabetes (odds ratios: Asia 2.24, Latin America 3.55, and Eastern Europe 2.42). In type 2 diabetes, short disease duration (Asia 0.97, Latin America 0.97, and Eastern Europe 0.82) and treatment with few oral glucose–lowering drugs (Asia 0.64, Latin America 0.76, and Eastern Europe 0.62) were predictors. Other region-specific factors included lack of microvascular complications and old age in Latin America and Asia; health insurance coverage and specialist care in Latin America; lack of obesity and self-adjustment of insulin dosages in Asia; and training by a diabetes educator, self-monitoring of blood glucose in patients who self-adjusted insulin, and lack of macrovascular complications in Eastern Europe. CONCLUSIONS—In developing countries, factors pertinent to patients, doctors, and health care systems all impact on glycemic control.

Mutations in PYCR1 cause cutis laxa with progeroid features

Abstract: Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.

Particle swarm optimization approach to portfolio optimization

Abstract: The survey of the relevant literature showed that there have been many studies for portfolio optimization problem and that the number of studies which have investigated the optimum portfolio using heuristic techniques is quite high. But almost none of these studies deals with particle swarm optimization (PSO) approach. This study presents a heuristic approach to portfolio optimization problem using PSO technique. The test data set is the weekly prices from March 1992 to September 1997 from the following indices: Hang Seng in Hong Kong, DAX 100 in Germany, FTSE 100 in UK, S&P 100 in USA and Nikkei in Japan. This study uses the cardinality constrained mean-variance model. Thus, the portfolio optimization model is a mixed quadratic and integer programming problem for which efficient algorithms do not exist. The results of this study are compared with those of the genetic algorithms, simulated annealing and tabu search approaches. The purpose of this paper is to apply PSO technique to the portfolio optimization problem. The results show that particle swarm optimization approach is successful in portfolio optimization.

Evaluation of morphometric parameters of drainage networks derived from topographic maps and DEM in point of floods

Abstract: An evaluation of morphometric parameters of two drainage networks derived from different sources was done to determine the influence of sub-basins to flooding on the main channel in the Havran River basin (Balikesir-Turkey). Drainage networks for the sub-basins were derived from both topographic maps scaled 1:25.000 and a 10-m resolution digital elevation model (DEM) using geographic information systems (GIS). Blue lines, representing fluvial channels on the topographic maps were accepted as a drainage network, which does not depict all exterior links in the basin. The second drainage network was extracted from the DEM using minimum accumulation area threshold to include all exterior links. Morphometric parameters were applied to the two types of drainage networks at sub-basin levels. These parameters were used to assess the influence of the sub-basins on the main channel with respect to flooding. The results show that the drainage network of sub-basin 4—where a dam was constructed on its outlet to mitigate potential floods—has a lower influence morphometrically to produce probable floods on the main channel than that of sub-basins 1, 3, and 5. The construction of the dam will help reduce flooding on the main channel from sub-basin 4 but it will not prevent potential flooding from sub-basin 1, 3 and 5, which join the main channel downstream of sub-basin 4. Therefore, flood mitigation efforts should be considered in order to protect the settlement and agricultural lands on the floodplain downstream of the dam. In order to increase our understanding of flood hazards, and to determine appropriate mitigation solutions, drainage morphometry research should be included as an essential component to hydrologic studies.

Overweight in school-aged children and its relationship with demographic and lifestyle factors: Results from the WHO-Collaborative Health Behaviour in School-aged Children (HBSC) Study

Abstract: Objectives: To examine overweight prevalence and its association with demographic and lifestyle factors in 11–15 year olds in the HBSC 2005–2006 survey.

Iron deficiency anemia

Abstract: Demir eksikli¤i anemisi dunyada en s›k ve en yayg›n olarak gorulen anemidir. Ozellikle sut cocuklar› ve genc k›zlarda daha s›k gozlenir. Etioloji de¤ifliklik gostermekle birlikte, s›kl›kla demirden fakir beslenme, kan kay›plar› ve emilim bozukluklar› sonucu geliflir. Cocuklarda solukluk, kardiovaskuler ve norolojik belirtiler, pika, kafl›k t›rnak, glossit, anguler stomatit gibi epitel de¤ifliklikleri gibi belirtiler ile kendini gosterir. Tedavi oral veya parenteral demir ile yap›l›r. (Turk Ped Arfl 2009; 44 Ozel Say›: 14-8) Anahtar kelimeler: Demir eksikli¤i, pediatrik, tan›, tedavi

Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance

Abstract: Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%) unrelated cases of IGE using quantitative PCR or SNP arrays and confirmed by array comparative genomic hybridization analysis using probes specific to the 15q13.3 region. The inheritance of this lesion was tracked using family studies. Of the seven microdeletions identified in probands, three were de novo, two were transmitted from an unaffected parent and in two cases the parents were unavailable. Non-penetrance of the microdeletion was identified in 4/7 pedigrees and three pedigrees included other family members with IGE who lacked the 15q13.3 deletion. The odds ratio is 68 (95% confidence interval 29-181), indicating a pathogenic lesion predisposing to epilepsy with complex inheritance and incomplete penetrance for the IGE component of the phenotype in multiplex families.

Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease.

Abstract: Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal-dominant polycystic kidney disease (ADPKD). Hypertension is a common early symptom of ADPKD, and occurs in approximately 60% of patients before renal function has become impaired. Hypertension is associated with an increased rate of progression to end-stage renal disease and is the most important potentially treatable variable in ADPKD. Left ventricular hypertrophy, which is a powerful, independent risk factor for cardiovascular morbidity and mortality, also occurs frequently in patients with ADPKD. Both hypertension and left ventricular hypertrophy have important roles in cardiovascular complications in these individuals. Moreover, biventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima-media thickness, and impaired coronary flow velocity reserve are present even in young patients with ADPKD who have normal blood pressure and well-preserved renal function. These findings suggest that cardiovascular involvement starts very early in the course of ADPKD. Intracranial and extracranial aneurysms and cardiac valvular defects are other potential cardiovascular problems in patients with ADPKD. Early diagnosis and treatment of hypertension, with drugs that block the renin-angiotensin-aldosterone system, has the potential to decrease the cardiovascular complications and slow the progression of renal disease in ADPKD.

Ultrastructural Changes in Axons Following Exposure to Pulsed Radiofrequency Fields

Abstract: Pulsed radiofrequency (PRF) fields applied by an electrode to neural structures, such as the peripheral sensory nociceptor axons and dorsal root ganglion, are clinically effective in reducing pain and other neuropathic syndromes. However, a full understanding of the underlying mechanisms by which this occurs has not yet been clarified. In this study, PRF is applied to the afferent axons of the sciatic nerves of rats. A standard radiofrequency (RF) electrode and RF generator is used to apply the RF signal output to the sciatic nerve using standard PRF parameters that have been successfully used in clinical practice. The ultrastructure of the treated axons is observed after 10 days by electron microscopy. A control, sham application is simultaneously applied to the contralateral sciatic nerve to provide a statistical differential comparison. It is found that the internal ultrastructural components of the axons show microscopic damage after PRF exposure, including: abnormal membranes and morphology of mitochondria, and disruption and disorganization of microfilaments and microtubules. The damage appears to be more pronounced for C-fibers than for A-delta and A-beta fibers. The results are discussed in terms of internal electric field strengths and thermodynamic parameters.