Differential to Terminal Ileitis: Terminal Ileum Neuroendocrine Tumor Identified on Screening Colonoscopy.

Background: Asymptomatic patients at average risk of developing colorectal cancer are encouraged to undergo screening colonoscopy beginning at age 45 years. While ileal intubation is often considered the gold standard for a complete colonoscopy, the relatively low diagnostic yield has prevented widespread adoption. Small bowel cancers, including neuroendocrine tumors, may present incidentally as terminal ileitis on routine colonoscopy with terminal ileum intubation. Neuroendocrine tumors, the most common primary neoplasm of the small intestine, are often asymptomatic or present as nonspecific abdominal pain in the sixth or seventh decade of life. Case Report: A 51-year-old asymptomatic male with unremarkable physical examination underwent screening colonoscopy that revealed scattered ulcerations of the terminal ileum. Immunohistochemistry of the lesion was consistent with well-differentiated neuroendocrine tumor, World Health Organization Grade I. DOTATATE positron emission tomography/computed tomography demonstrated avid adjacent right mesenteric lymph node and avid focal pancreatic body lesion. Fine-needle biopsy and immunohistochemistry of the pancreatic lesion confirmed neuroendocrine tumor, while the mesenteric lymph node was found to be benign. The patient underwent robotic-assisted ileocolic resection and has ongoing surveillance of the pancreatic lesion. Conclusion: Terminal ileitis encompasses a host of pathologic processes, including inflammatory states, infectious disease, malignancy, and vasculitis. Importantly, small bowel cancer is an increasing cause of terminal ileitis. Screening colonoscopy with ileal intubation can be a valuable tool for early detection of these lesions.

Mixed fungaemia: an 18-year report from a tertiary-care university hospital and a systematic review.

BACKGROUND: While fungaemia caused by two or more different species of yeasts (mixed fungaemia, MF) is infrequent, it might be underestimated. AIMS: This study aimed to determine the incidence of MF, clinical characteristics of the patients, and antifungal susceptibility profiles of the isolates with a systematic review of the literature. SOURCES: Data sources were PubMed and Scopus. STUDY ELIGIBILITY CRITERIA: Studies reporting ten or more mixed fungaemia episodes. CONTENT: Study included MF episodes in adults between January 2000 and August 2018 in Hacettepe University Hospitals, Turkey. The isolation, identification and antifungal susceptibility testing (AFST) of the isolates were by standard mycological methods. Patient data were obtained retrospectively. Literature search was performed using relevant keywords according to PRISMA systematic review guidelines. A total of 32 patients with 33 MF episodes were identified. Among all fungaemia episodes, MF incidence was 3.7% (33/883). All patients had one or more underlying disorders among which solid-organ cancer (50.0%, 16/32) was the most common. Overall mortality was 51.5% (17/33). The most preferred antifungal agents for initial treatment were fluconazole (48.5%, 16/33) and echinocandins (39.4%, 13/33). Fluconazole susceptible-dose-dependent (S-DD) or -resistant Candida species were detected in 15 episodes, and an isolate of C. parapsilosis was classified as S-DD by AFST. All Candida isolates were susceptible to echinocandins. Non-candida yeasts with intrinsic resistance/reduced susceptibility to both echinocandins and fluconazole were detected in two episodes. Systematic review of the literature revealed 24 studies that reported more than ten MF episodes. Methodology was variable. Improvement of detection rates was reported when chromogenic agars were used. Most studies underlined detection of isolates with reduced susceptibility. IMPLICATIONS: Although rare, the MF rate is affected by the detection methods, which have improved in recent years. Fluconazole and echinocandins were used for initial treatment in accordance with the current guideline recommendations; however, isolates non-susceptible to both were detected. Detection of a mixed infection offers an opportunity for optimum treatment.

Oxidative Stress and Mitochondrial Abnormalities Contribute to Decreased Endothelial Nitric Oxide Synthase Expression and Renal Disease Progression in Early Experimental Polycystic Kidney Disease.

Vascular abnormalities are the most important non-cystic complications in Polycystic Kidney Disease (PKD) and contribute to renal disease progression. Endothelial dysfunction and oxidative stress are evident in patients with ADPKD, preserved renal function, and controlled hypertension. The underlying biological mechanisms remain unknown. We hypothesized that in early ADPKD, the reactive oxygen species (ROS)-producing nicotinamide adenine dinucleotide phosphate hydrogen (NAD(P)H)-oxidase complex-4 (NOX4), a major source of ROS in renal tubular epithelial cells (TECs) and endothelial cells (ECs), induces EC mitochondrial abnormalities, contributing to endothelial dysfunction, vascular abnormalities, and renal disease progression. Renal oxidative stress, mitochondrial morphology (electron microscopy), and NOX4 expression were assessed in 4- and 12-week-old PCK and Sprague-Dawley (wild-type, WT) control rats (n = 8 males and 8 females each). Endothelial function was assessed by renal expression of endothelial nitric oxide synthase (eNOS). Peritubular capillaries were counted in hematoxylin-eosin (H&E)-stained slides and correlated with the cystic index. The enlarged cystic kidneys of PCK rats exhibited significant accumulation of 8-hydroxyguanosine (8-OHdG) as early as 4 weeks of age, which became more pronounced at 12 weeks. Mitochondria of TECs lining cysts and ECs exhibited loss of cristae but remained preserved in non-cystic TECs. Renal expression of NOX4 was upregulated in TECs and ECs of PCK rats at 4 weeks of age and further increased at 12 weeks. Contrarily, eNOS immunoreactivity was lower in PCK vs. WT rats at 4 weeks and further decreased at 12 weeks. The peritubular capillary index was lower in PCK vs. WT rats at 12 weeks and correlated inversely with the cystic index. Early PKD is associated with NOX4-induced oxidative stress and mitochondrial abnormalities predominantly in ECs and TECs lining cysts. Endothelial dysfunction precedes capillary loss, and the latter correlates with worsening of renal disease. These observations position NOX4 and EC mitochondria as potential therapeutic targets in PKD.

Non-HACEK Gram-negative bacillus endocarditis.

PATIENTS AND METHODS: Retrospective analysis of clinical data using 26 diagnosed non-HACEK Gram-negative infective endocarditis cases from nine hospitals in Turkey. RESULTS: Mean age of patients was 53 (28-84) years, with a 23% case fatality. Nineteen (73%) of the 26 patients had at least one predisposing factor. The presence of a central venous catheter was the most common predisposing factor (7/26 patients). Pseudomonasaeruginosa (7/26 patients) and Escherichiacoli (7/26 patients) were the most common pathogens. The median duration of the antibiotic therapy was 42 days (range 3-84 days). Surgical procedures were performed in 10 patients. The case fatality was similar in patients who did or did not undergo surgery (20% vs. 25%).

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function.

INTRODUCTION: Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfecta murine (oim) and +/G610C. METHODS: Wild-type (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with Tris-buffered saline (vehicle) or sActRIIB-mFc and their hindlimb muscles evaluated for mass, morphology, and contractile function. RESULTS: sActRIIB-mFc-treated WT, +/G610C, and oim/oim mice had increased hindlimb muscle weights and myofiber cross-sectional area compared with vehicle-treated counterparts. sActRIIB-mFc-treated oim/oim mice also exhibited increased contractile function relative to vehicle-treated counterparts. DISCUSSION: Blocking endogenous ActRIIB was effective at increasing muscle size in mouse models of OI, and increasing contractile function in oim/oim mice. ActRIIB inhibitors may provide a potential mutation-specific therapeutic option for compromised muscle function in OI. Muscle Nerve 57: 294-304, 2018.

Sofosbuvir/velpatasvir regimen promises an effective pan-genotypic hepatitis C virus cure.

Hepatitis C virus (HCV) is a global pandemic, with nearly 200 million infected patients worldwide. HCV is the most common blood-borne infection in the US with numerous health implications including liver fibrosis, cirrhosis, and hepatocellular cancer. Traditional genotype-based HCV therapies with interferon resulted in moderate success in the sustained elimination of viral genome. Recent clinical trials of the once-daily combination tablet of sofosbuvir, a nonstructural (NS) 5B polymerase inhibitor, and velpatasvir, an NS5A inhibitor, demonstrate sustained virologic response rates of about 95%, regardless of prior treatment experience or presence of cirrhosis across all HCV genotypes. Patients reported improvements in general health, fatigue, and emotional and mental well-being after completing combination therapy. The combination treatment is effective, but does need to be administered with caution in patients receiving certain medications or with certain diseases. Herein, we review the safety and efficacy of sofosbuvir/velpatasvir combination regimen for all HCV genotypes.

Ongoing activity of Toscana virus genotype A and West Nile virus lineage 1 strains in Turkey: a clinical and field survey.

Toscana virus (TOSV), West Nile virus (WNV) and tickborne encephalitis virus (TBEV) are among major viral pathogens causing febrile disease and meningitis/encephalitis. The impact of these viruses was investigated at a referral centre in Ankara Province, Central Anatolia in 2012, where previous reports suggested virus circulation but with scarce information on clinical cases and vector activity. Serum and/or cerebrospinal fluid samples from 94 individuals were evaluated, in addition to field-collected arthropod specimens that included 767 sandflies and 239 mosquitoes. Viral nucleic acids in clinical samples and arthropods were sought via specific and generic nested/real-time PCRs, and antibody responses in clinical samples were investigated via commercial indirect immunofluorescence tests (IIFTs) and virus neutralization. A WNV antigen assay was also employed for mosquitoes. WNV neuroinvasive disease has been identified in a 63-year-old male via RNA detection, and the WNV strain was characterized as lineage 1. TOSV infections were diagnosed in six individuals (6.3%) via RNA or IgM detection. Partial sequences in a 23-year-old female, presented with fever and transient pancytopenia, were characterized as TOSV genotype A. Febrile disease with arthralgia and/or peripheral cranial nerve involvement was noted in cases with TOSV infections. Previous WNV and TOSV exposures have been observed in 5.3% and 2.1% of the subjects, respectively. No confirmed TBEV exposure could be identified. Morphological identification of the field-collected mosquitoes revealed Culex pipiens sensu lato (74.4%), Anopheles maculipennis (20.9%), An. claviger (2.1%) and others. Sandfly species were determined as Phlebotomus papatasi (36.2%), P. halepensis (27.3%), P. major s. l. (19.3%), P. sergenti (8.9%), P. perfiliewi (4.4%), P. simici (2.6%) and others. Viral infections in arthropods could not be demonstrated. TOSV genotype A and WNV lineage 1 activity have been demonstrated as well as serologically proven exposure in patients. Presence of sandfly and mosquito species capable of virus transmission has also been revealed.

Assessing changes in oral health-related quality of life following dental rehabilitation under general anesthesia.

OBJECTIVE: To determine whether dental treatment under general anesthesia (GA) improved oral health-related quality of life (OHRQoL) in pre-school children, to evaluate the sensitivity and responsiveness of the Turkish version of the Early Childhood Oral Health Impact Scale (ECOHIS) and to examine parental satisfaction with the care received. STUDY DESIGN: The parents/caregivers of 120 pre-school children receiving dental treatment under GA, were asked to complete the ECOHIS before and after treatment. Participants were also asked a global transition judgement concerning change in their child's condition after treatment. Global transition judgement and distribution changes in ECOHIS scores were used to assess the sensitivity and responsiveness. RESULTS: 98 children completed the follow-up survey. Between pre- and post-treatment ECOHIS scores, significant reduction was observed (p < 0.001). The effect sizes were moderate and large (0.36 to 1.63). Global transition rating groups were compatible with statistical differences between pre- and posttreatment scores, supporting the responsiveness of the ECOHIS. 91% of parents regarded the experience to be positive. CONCLUSIONS: Children's OHRQoL showed significant improvement after treatment. The majority ofparents reported a high degree of satisfaction. Also, Turkish version of the ECOHIS was sensitive to dental treatment under GA for pre-school children and responsive to treatment-associated changes.

Supraorbital and infraorbital nerve blockade in migraine patients: results of 6-month clinical follow-up.

BACKGROUND: Nerve blockades are used for the treatment of acute migraine episodes in emergency room conditions and beneficial results are obtained from this clinical use. Although this is the case, there are limited numbers of studies investigating the long-term effects of such an approach. PATIENTS AND METHODS: In this investigation, we had 26 patients diagnosed as migraine based on the ICHD II criteria, these were injected with 1% lidocaine at supraorbital and infraorbital nerve localizations and clinical results were evaluated after 6 months of follow-up. All patients received 1.5 ml of 1% lidocaine bilaterally for supraorbital and infraorbital nerves with three day intervals for three times. Clinical evaluation was conducted by recording the number of migraine episodes per month together with migraine disability assessment scale (MIDAS) and visual analog scale (VAS) scores before and six months after the treatment. RESULTS:  Mean age of the patients recruited in the study was 31.1±10.2 years. Disease duration was 8.1±5.4 years, the duration of the headache was 28.4±18.4 hours, mean number of episodes before treatment was 9.9±5.2, mean MIDAS was calculated as 3.2±0.8, and VAS as 9.0±1.0. Six months after the treatment, mean number of attacks was 2.0±3.0, MIDAS was 1.4±0.9 and VAS was 3.5±3.6. There was a statistically significant difference between the results obtained before and after the treatment. CONCLUSIONS:  Injecting 1% of lidocaine to supraorbital and infraorbital nerve for three times prevents the acute migraine episodes effectively during the 6-months of follow-up without having any significant side effects.

Community-acquired acute bacterial meningitis in the elderly in Turkey.

This investigation aimed both to delineate the current status of community-acquired acute bacterial meningitis and to produce data on the interrelationships between clinical, laboratory and therapeutic parameters in the elderly. This retrospective cohort study was conducted in 28 Turkish institutions in 159 culture-positive patients over the age of 50 years. Streptococcus pneumoniae was the most common pathogen (69.2%), followed by Listeria monocytogenes (8.8%). For this reason, antilisterial antibiotics such as ampicillin or benzylpenicillin should be added to the therapeutic regimen. Pathogen-specific mortality did not vary between S. pneumoniae and L. monocytogenes. The overall mortality was 2.5% at the third day, 12.6% at the seventh day, 20.1% at the 14th day and 21.4% at the 21st day. The risk factors for fatality were increasing age, the presence of stupor, sepsis and inappropriate antibiotic administration. Cerebrospinal fluid (CSF) leukocyte counts and CSF/blood glucose ratios were lower in patients who died. Fever did not differ between survivors and fatal cases. The mean duration of antibiotic therapy in survivors was 16.3 +/- 6.4 days. One-fifth of the patients had complications, and in 5.7% of the patients sequelae persisted at follow-up.

Oxidative and antioxidative balance in patients of migraine.

BACKGROUND: Migraine is characterized by multiple attacks of severe headaches often unilateral. The molecular mechanisms of migraine have not yet been clearly defined. Disorders of oxidant-antioxidant balance are observed in a number of acute and chronic diseases of the central nervous system. Oxidative stress is also believed to play a role in the pathogenesis of migraine. To the best of our knowledge, this is the first study investigating oxidant and antioxidant status of patients having migraine without aura (MWoA) and comparing them with those of age and sex matched healthy controls (CG). METHODS: We evaluated the Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) of the plasma and Oxidative Stress Index (OSI) using a recently measurement method developed by Erel. RESULTS: Seventy five patients (55 Female, 20 Male) having MWoA who are free of attacks and 65 healthy volunteers (41 Female, 24 Male) (CG) were enrolled in this research. Mean age of the patients with MWoA and the control group were calculated (30.94 +/- 10.37 vs 31.0 +/- 9.46 years respectively; p > 0.05). Serum TAS levels of patients with MWoA were significantly lower than those of healthy controls (0.72 +/- 0.008 vs. 0.80 +/- 0.179 micromol Trolox equivalent/L; p < 0.001). Conversely, serum TOS values were significantly higher in patients with MWoA than in CG (15.39 +/- 0.770 vs.13.01 +/- 0.471 pmol H2O2 equivalent/L; P < 0.001). The mean values of OSI were greater in patients than in controls (1.75 +/- 0.59 vs. 1.56 +/- 0.57, p < 0.023). Total SH levels were significantly higher in the control group (MWoA: 0.24 +/- 0.005; CONTROLS: 0.28 +/- 0.005, p = 0.001). Furthermore, there was a negative correlation between the levels of Total SH and the duration of the headaches (r: -0.426, p < 0.001). Likewise; there was a positive correlation between OSI and the frequency of the headaches (r: 0.123, p < 0.002). CONCLUSIONS: In this study, we demonstrated that the levels of total antioxidants were decreased and the levels of total oxidants and the oxidative stress index were increased in patients with MWoA. These findings may be an evidence of exposure to potent oxidative stress in MWoA patients. Further investigations are required to clarify the role of oxidative stress in the etiopathogenesis of MWoA.

Efficacy of nasopharyngeal culture in identification of pathogen in middle ear fluid in chronic otitis media with effusion.

PURPOSE: Chronic otitis media with effusion (OME) is the leading cause of hearing loss during childhood. In bacterial etiology of OME, the most frequent pathogens responsible are Haemophilus influenzae followed by Streptococcus pneumoniae and Moraxella catarrhalis. This study aimed at evaluating the accuracy of nasopharyngeal (NP) specimens in the identification of pathogens in the middle ear fluid (MEF) in patients with OME. MATERIALS AND METHODS: In this cross sectional, case-control study, 95 MEFs and 53 NP secretion specimens were obtained from 53 children. As a control group, 102 NP specimens were taken from children having an operation other than an otological disease. Conventional culture methods and multiplex-PCR method have been used to determine the etiology of OME; NP carriage between cases and control groups were compared using conventional culture methods. Pearson Chi-Square and Fisher's Exact tests were used in statistical analysis. RESULTS: Bacteria were isolated by culture in 37.9% of MEF specimens, 14.7% of which belonged to the group H. influenzae, S. pneumoniae and M. catarrhalis. PCR was positive in 30.5% specimens targeting the same pathogens. There was a two-fold increase in carriage rate of S. pneumoniae and H. influenzae in patients than controls for each pathogen. CONCLUSION: PCR is a more reliable method to detect middle ear pathogens in MEF in comparison with the conventional culture methods. The NP colonization wasn't found to be an indicator of the pathogen in MEF although middle ear pathogens colonize more in nasopharynx of diseased children.

Investigation of oral selegiline and rasagiline administration on QT interval in conscious rabbits.

Rasagiline (RSG) and selegiline (SEL) are potent selective monoamine oxidase-B inhibitors and used in the treatment of Parkinson's disease. Selegiline is metabolized in vivo to I-methamphetamine and I-amphetamine which effect cardiovascular system. Therefore, the aim of this study was to evaluate and to compare the effects of long-term use of these drugs on QT interval in conscious rabbits. The study involved 17 New Zealand rabbits of both sexes, aged between 7 and 14 months. Control group (CG, n = 6) was orally given isotonic saline solution at dose of 0.5 cc/per rabbit. The SEL group (SG, n = 6) received 5 mg/per rabbit SEL orally twice daily (09:00 am and 09:00 pm) for 14 days. The RSG group (RG, n = 5) was orally given of RSG at 1 mg/per rabbit daily for 14 days. Electrocardiographic records were taken before the experiment (baseline) and at 1st, 7th, and 14th days of experiment by direct writing electrocardiograph for two groups. Heart rate (HR), QT and QTc values were determined from ECG records. HR did not significantly differ in both treatment groups through the experimental period when compared to baseline values. The significant prolongation of QT and QTc values were observed at 7th, and 14th day (p < 0.01) in SG and 1st day of experiment in RG (p < 0.05) as compared to baseline values. In conclusion, the results obtained suggest a statistically significant effect of SEL on QTc prolongation when compared to RAS. QTc prolongations should be taken into account in Parkinson's disease where autonomic system is involved.

Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits.

Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive therapy for partial seizures in patients. Although many neuro-psychiatric and non-cardiac drugs are known to prolong ventricular repolarization as manifested by QTc prolongation on ECG of which provokes torsades de pointes, there is limited data available regarding the characteristics of QT interval in conscious laboratory animals after PRG administration. For that purpose, effects of different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and QTc values in rabbits were evaluated at a predefined time interval in this research. The study involved 28 New Zealand rabbits of both sexes, aged between 8 and 12 months. Animals were divided into four equal groups. Rabbits in control group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, respectively. ECG records were taken before experiment (baseline) and at 1st, 2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph. HR, QT and QTc values were determined from ECG records. Heart rates increased in all groups when compared to baseline values. The increases were evident at 4th h in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III compared with CG. After application of PRG, QTc began to prolong at 1st h through the 4th of experiment and then turned to baseline values at 6th h of the experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and 4th h (p < 0.001) of application in group III were significantly different from CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time and dose dependent (p < 0.001). Increase in HR and QTc prolongation determined in PRG given rabbits may implied that clinicians should take care of these changes when using this drug and further studies are required to fully understand the mechanism involved.

Photophysical and complexation properties of benzenesulfonamide derivatives with different donor and acceptor moieties.

Pyrrolobenzosulfonamide, indolobenzosulfonamide and carbazolobenzosulfonamide derivatives with different acceptor groups were synthesized and their photophysical properties were compared. The electron donor linking sites are found to influence the emission characteristics of these compounds while acceptor linking sites have no noticeable effects on the spectral properties. P2-A5 which is a C-C linked pyrrole derivative exhibited different spectral properties from the C-N linked pyrrole derivatives. The complexation properties of the molecules were also investigated employing Na (I), Ca (II), Li (I), Mg (II), Zn (II) and Cu (II) ions.

Sildenafil improves hemodynamic parameters in COPD--an investigation of six patients.

Pulmonary hypertension (PH) is an important predictor of mortality in chronic obstructive pulmonary disease (COPD). The phosphodiesterase 5 inhibitor sildenafil has been demonstrated to reduce pulmonary arterial pressure (PAP) in different diseases. We wanted to investigate the effect of sildenafil on hemodynamic parameters and the 6-min walk test (6 MWT) in six patients with severe COPD and echocardiographically estimated PH. A 6 MWT was performed and hemodynamic parameters were measured by right heart catheterization before and 1 and 12h after injection of 50mg sildenafil intravenously. A 3-months period of peroral sildenafil therapy 50mg twice daily followed and finally hemodynamic parameters and a 6 MWT were repeated. Intravenously applied sildenafil could be demonstrated to reduce PAP and pulmonary vasculature resistance (PVR) significantly. And after 3 months of oral sildenafil, the mean PAP has decreased from 30.2+/-5.5 mmHg (range: 24-39 mmHg) to 24.6+/-4.2 mmHg (range: 20-30 mmHg) (p=0.01). The PVR has decreased from 401+/-108 dyn s cm(-5) (range: 266-558 dyn s cm(-5)) to 264+/-52 dyn s cm(-5) (range: 204-333 dyn s cm(-5)) (p<0.05). Physical conditions improved: the 6-min walk distance increased from 351+/-49 to 433+/-52 m. In conclusion, in six patients suffering from severe COPD we could demonstrate significantly improved hemodynamic parameters after 50 mg sildenafil intravenous application. And after 3 months of oral sildenafil, walking distance in the 6 MWT increased significantly as well as hemodynamic parameters in the five patients who had accepted a second right heart catheterization.