Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients.

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how microstructural degeneration is linked to dopaminergic loss is also uncertain. In this study, thirty de novo PD patients and twenty healthy subjects (HS) underwent 6-[18F]-fluoro-L-dopa (FDOPA) PET and MRI studies no later than 12 months from clinical diagnosis. FDOPA uptake rate (Ki), fractional volume of free-water (FW), and iron-sensitive R2* relaxometry were quantified within nigrostriatal regions. Inter-group differences (PD vs HS) were studied using non-parametric statistics and complemented with Cohen's d effect sizes and Bayesian statistics. Correlation analyses were performed exploring biomarker dependencies and their association with bradykinesia scores. PD patients exhibited a significant decline in nigrostriatal dopaminergic activity, being post-commissural putamen (-67%) and posterolateral SNc (-11.7%) the most affected subregions within striatum and SNc respectively. Microstructural alterations (FW) were restricted to the hemisphere corresponding to the most affected side and followed similar spatial gradients as FDOPA Ki (+20% in posterior putamen and +11% in posterolateral SNc). R2* revealed no relevant significant changes. FDOPA and FW were correlated within the posterolateral SNc, and clinical severity was associated with FDOPA Ki loss. The asymmetry between striatal and SNc changes for both dopaminergic depletion and microstructural degeneration biomarkers is consistent with a neurodegenerative process that begins in the striatal terminals before progressing toward the cell bodies in the SNc.

Impact of new technologies on neurology in Spain. Review by the New Technologies Ad-Hoc Committee of the Spanish Society of Neurology.

INTRODUCTION: New technologies are increasingly widespread in biomedicine. Using the consensus definition of new technologies established by the New Technologies Ad-Hoc Committee of the Spanish Society of Neurology (SEN), we evaluated the impact of these technologies on Spanish neurology, based on communications presented at Annual Meetings of the SEN. MATERIAL AND METHODS: We defined the concept of new technology in neurology as a novel technology or novel application of an existing technology, characterised by a certain degree of coherence persisting over time, with the potential to have an impact on the present and/or future of neurology. We conducted a descriptive study of scientific communications presented at the SEN's annual meetings from 2012 to 2018, analysing the type of technology, the field of neurology, and the geographical provenance of the studies. RESULTS: We identified 299 communications related with new technologies from a total of 8139 (3.7%), including 120 posters and 179 oral communications, ranging from 1.6% of all communications in 2012 to 6.8% in 2018. The technologies most commonly addressed were advanced neuroimaging (24.7%), biosensors (17.1%), electrophysiology and neurostimulation (14.7%), and telemedicine (13.7%). The neurological fields where new technologies were most widely employed were movement disorders (18.4%), cerebrovascular diseases (15.7%), and dementia (13.4%). Madrid was the region presenting the highest number of communications related to new technologies (32.8%), followed by Catalonia (26.8%) and Andalusia (9.0%). CONCLUSIONS: The number of communications addressing new technologies follows an upward trend. The number of technologies used in neurology has increased in parallel with their availability. We found scientific communications in all neurological subspecialties, with a heterogeneous geographical distribution.

Impact of new technologies on neurology in Spain. Review by the New Technologies Ad-Hoc Committee of the Spanish Society of Neurology. / Impacto de las nuevas tecnologías en la neurología en España. Revisión del Comité Ad-Hoc de Nuevas Tecnologías de la Sociedad Española de Neurología.

INTRODUCTION: New technologies (NT) are increasingly widespread in biomedicine. Using the consensus definition of NT established by the New Technologies Ad-Hoc Committee of the Spanish Society of Neurology (SEN), we evaluated the impact of these technologies on Spanish neurology, based on communications presented at Annual Meetings of the SEN. MATERIAL AND METHODS: We defined the concept of NT in neurology as a novel technology or novel application of an existing technology, characterised by a certain degree of coherence persisting over time, with the potential to have an impact on the present and/or future of neurology. We conducted a descriptive study of scientific communications presented at the SEN's annual meetings from 2012 to 2018, analysing the type of NT, the field of neurology, and the geographical provenance of the studies. RESULTS: We identified 299 communications related with NT from a total of 8,139 (3.7%), including 120 posters and 179 oral communications, ranging from 1.6% of all communications in 2012 to 6.8% in 2018. The technologies most commonly addressed were advanced neuroimaging (24.7%), biosensors (17.1%), electrophysiology and neurostimulation (14.7%), and telemedicine (13.7%). The neurological fields where NT were most widely employed were movement disorders (18.4%), cerebrovascular diseases (15.7%), and dementia (13.4%). Madrid was the region presenting the highest number of communications related to NT (32.8%), followed by Catalonia (26.8%) and Andalusia (9.0%). CONCLUSIONS: The number of communications addressing NT follows an upward trend. The number of NT used in neurology has increased in parallel with their availability. We found scientific communications in all neurological subspecialties, with a heterogeneous geographical distribution.

Oral health conditions in Wilson's disease patients: A clinical diagnostic study.

AIM: The aims of this study were: To evaluate oral health conditions, oral health behaviours and eating habits in Wilson's disease (WD) patients; to assess the possible relationship between oral health status and long-term pharmacological therapies undertaken. METHODS: Sixty WD patients were selected and their data were compared to those of an age-matched control group of 62 subjects. Clinical examinations were carried out and a questionnaire on oral health behaviours and eating habits was submitted to both groups. WD patients were interviewed on long-term pharmacological therapies undertaken. Statistical analysis was performed. RESULTS: The mean DMFT value was 3.75±4.65 in the WD group and 2.81±4.65 in the control group. The difference in the mean DMFT value between the two groups was not statistically significant. Modified Dental Enamel Defects (DDE) Index showed significantly higher values in WD group than in control group. No statistical differences in Visible Plaque Index (VPI), Gingival Bleeding Index (GBI) and malocclusions were observed between groups. In relation to the questionnaire, the differences between groups were statistically significant for: dental visits in a year; brushing teeth after a snack; drinking soft beverages; using mouthwash. For WD patients no statistical correlation between oral health status and long-term pharmacological therapies undertaken was observed. CONCLUSION: WD patients did not show worse oral health conditions than the control group, despite worse oral health behaviours and eating habits. Nerveless, WD patients showed higher presence of dental enamel defects. Finally, for WD group oral health status was not correlated to the long-term pharmacological therapies.

Author Correction: Computer keyboard interaction as an indicator of early Parkinson's disease.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effect of nutrient deprivation on the expression and the epigenetic signature of sirtuin genes.

BACKGROUND AND AIM: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes. METHODS AND RESULTS: We performed these studies in mouse hepatoma cells, that were grown in standard medium, or in media containing low glucose concentration, or no glucose, or no amino acids. We applied quantitative real-time PCR to cDNA, methylation-enriched DNA and nuclease-treated DNA in order to evaluate gene expression, DNA methylation, and chromatin condensation, respectively. This study shows that the expression of sirtuin genes varies following nutrient deprivation. Moreover, we observed that changes of DNA methylation and chromatin condensation occur at the transcription start site of sirtuin genes following nutrient deprivation. CONCLUSIONS: Epigenetic mechanisms may have a role in the sirtuin response to nutrient deprivations in cultured hepatoma cells. Replicating these results in vivo to achieve a comprehensive understanding of the epigenetic control of sirtuin expression following nutrient deprivations might open up novel therapeutic possibilities to cure metabolic diseases and promote human health.

Computer keyboard interaction as an indicator of early Parkinson's disease.

Parkinson's disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61).

Genome-Wide DNA Methylation Analysis Identifies Novel Hypomethylated Non-Pericentromeric Genes with Potential Clinical Implications in ICF Syndrome.

INTRODUCTION AND RESULTS: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive disease, characterized by severe hypomethylation in pericentromeric regions of chromosomes (1, 16 and 9), marked immunodeficiency and facial anomalies. The majority of ICF patients present mutations in the DNMT3B gene, affecting the DNA methyltransferase activity of the protein. In the present study, we have used the Infinium 450K DNA methylation array to evaluate the methylation level of 450,000 CpGs in lymphoblastoid cell lines and untrasformed fibroblasts derived from ICF patients and healthy donors. Our results demonstrate that ICF-specific DNMT3B variants A603T/STP807ins and V699G/R54X cause global DNA hypomethylation compared to wild-type protein. We identified 181 novel differentially methylated positions (DMPs) including subtelomeric and intrachromosomic regions, outside the classical ICF-related pericentromeric hypomethylated positions. Interestingly, these sites were mainly located in intergenic regions and inside the CpG islands. Among the identified hypomethylated CpG-island associated genes, we confirmed the overexpression of three selected genes, BOLL, SYCP2 and NCRNA00221, in ICF compared to healthy controls, which are supposed to be expressed in germ line and silenced in somatic tissues. CONCLUSIONS: In conclusion, this study contributes in clarifying the direct relationship between DNA methylation defect and gene expression impairment in ICF syndrome, identifying novel direct target genes of DNMT3B. A high percentage of the DMPs are located in the subtelomeric regions, indicating a specific role of DNMT3B in methylating these chromosomal sites. Therefore, we provide further evidence that hypomethylation in specific non-pericentromeric regions of chromosomes might be involved in the molecular pathogenesis of ICF syndrome. The detection of DNA hypomethylation at BOLL, SYCP2 and NCRNA00221 may pave the way for the development of specific clinical biomarkers with the aim to facilitate the identification of ICF patients.

Urethral sphincter innervation and clitoral blood flow after the transobturator (TOT) approach.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to exclude neurovascular damage due to prosthetic mini-invasive surgery using transobturator tape (TOT) by pre- and postoperative electromyography (EMG) of the striated urethral sphincter and a color Doppler ultrasonography evaluation of clitoral blood flow. METHODS: A total of 25 women affected by clinical stress urinary incontinence (SUI) were enrolled. After undergoing urodynamic assessment, pelvic organ prolapse quantification, urine culture, Q-tip test, and stress test, each subject underwent color Doppler ultrasonography to record clitoral blood flow and EMG of the urethral sphincter with a needle electrode inserted through the mucosa into the muscle tissue before surgery. A single urogynecologist performed the TOT surgical technique for the treatment of all patients. Urogynecologic examination, EMG, and color Doppler ultrasound follow-up were performed at 1 and 6 months after surgery. RESULTS: At the urogynecologic examination performed 1 and 6 months after the TOT approach the stress test was negative, urethral hypermobility was reduced, and sling exposure was not observed for each patient. There was no statistically significant difference in electromyographic values (p > 0.05) in both the follow-ups with regard to baseline values. Pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) values increased during the first follow-up (p < 0.01); PI and RI values increased during the second follow-up with respect to baseline values (p < 0.01) CONCLUSIONS: TOT prosthesis surgery, avoiding denervation and devascularization of pelvic structures, does not damage the urethral sphincter.

Vascular smooth muscle cell dysfunction in patients with migraine.

BACKGROUND: Migraine is associated with increased risk of cardiovascular disease, but the mechanisms are unclear. OBJECTIVE: To investigate the activity of endothelial and vascular smooth muscle cells (VSMCs) in patients with migraine. METHODS: Case-control study of 12 patients with migraine without aura and 12 matched healthy control subjects. Endothelial and VSMC components of vascular reactivity were explored by plethysmography measurement of forearm blood flow (FBF) during infusions of vasoactive agents into the brachial artery. Forearm production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was also quantified. RESULTS: In patients with migraine, the vasodilating effect of acetylcholine (ACh), an endothelium-dependent vasodilator, was markedly reduced (p < 0.001 by analysis of variance). In response to the highest dose of ACh, FBF rose to 8.6 +/- 2.2 in patients with migraine and to 22.7 +/- 3.0 mL x dL(-1) x min(-1) in controls (p = 0.001). The dose-response curve to nitroprusside, a vasodilator directly acting on VSMCs, was depressed in patients with migraine (p < 0.001 by analysis of variance). The maximal response of FBF to nitroprusside was 12.1 +/- 2.0 in patients with migraine and 24.1 +/- 1.8 mL x dl(-1) x min(-1) in controls (p < 0.001). During ACh infusion, NO release from the endothelium was similar in patients and controls. In contrast, there was a marked release of cGMP from VSMCs in controls, but not in patients with migraine (-1.9 +/- 2.2 in patients with migraine and -19.1 +/- 5.4 nmol x dL(-1) x min(-1) in controls; p = 0.03). CONCLUSIONS: Patients with migraine are characterized by a distinct vascular smooth muscle cell dysfunction, revealed by impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation.

The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1- and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.

Lessons from two human chromatin diseases, ICF syndrome and Rett syndrome.

Spatial organisation of DNA into chromatin profoundly affects gene expression and function. The recent association of genes controlling chromatin structure to human pathologies resulted in a better comprehension of the interplay between regulation and function. Among many chromatin disorders we will discuss Rett and immunodeficiency, centromeric instability and facial anomalies (ICF) syndromes. Both diseases are caused by defects related to DNA methylation machinery, with Rett syndrome affecting the transduction of the repressive signal from the methyl CpG binding protein prototype, MeCP2, and ICF syndrome affecting the genetic control of DNA methylation, by the DNA methyltransferase DNMT3B. Rather than listing survey data, our aim is to highlight how a deeper comprehension of gene regulatory web may arise from studies of such pathologies. We also maintain that fundamental studies may offer chances for a therapeutic approach focused on these syndromes, which, in turn, may become paradigmatic for this increasing class of diseases.

Multiple binding of methyl-CpG and polycomb proteins in long-term gene silencing events.

Epigenetic regulation is involved in the maintenance of long-term silencing phenomena, such as X-inactivation and genomic imprinting in mammals. Gene repression is mediated by several mechanisms, such as histone modifications, DNA methylation, and recruitment of Polycomb proteins. To understand the mechanistic relationships between these mechanisms for stable gene silencing, we analyzed the mechanisms of X- and Y-inactivation of the PAR2 gene SYBL1, previously showed to be regulated by concerted epigenetic mechanisms. Maintenance of stable repression occurs via the recruitment of both MBDPs and PRC2 complexes to SYBL1 promoter. Their binding is equally sensitive to defective DNA methylation seen in cells derived from ICF syndrome patients. Multiple occupancy is a feature shared within long-term repressed genes, such as the X-inactivated PGK1 and the imprinted IGF2. MBD2, MBD3, and MeCP2 occupy SYBL1 promoter simultaneously, as revealed by sequential ChIP. We did not find this co-occurring binding when looked for members of PRC2 complex together with any of the methyl-binding proteins. Furthermore, in co-transfection assays, MECP2 can silence methylated SYBL1 promoter, whereas the mutated protein fails. However, RNA interference of endogenous MECP2 does not induce the expression of the inactive SYBL1 alleles, suggesting that its silencing activity can be replaced by the other methyl-binding proteins. Our data suggest that maintenance of long-term silencing involves multiple layers of epigenetic control functionally redundant. PRC2 and MBD proteins could collaborate to different phases of this process, the former possibly recruiting DNMTs to the silenced promoters, the latter dictating the lock of the transcription.

Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications.

Maintenance of X-inactivation is achieved through a combination of different repressive mechanisms, thus perpetuating the silencing message through many cell generations. The second human X-Y pseudoautosomal region 2 (PAR2) is a useful model to explore the features and internal relationships of the epigenetic circuits involved in this phenomenon. Recently, we demonstrated that DNA methylation plays an essential role for the maintenance of X- and Y-inactivation of the PAR2 gene SYBL1; here we report that the silencing of the second repressed PAR2 gene, SPRY3, appears to be independent of DNA methylation. In contrast to SYBL1, the inactive X and Y alleles of SPRY3 are not reactivated in cells treated with a DNA methylation inhibitor and in cells from ICF (immunodeficiency, centromeric instability, facial anomalies) syndrome patients, which have mutations in the DNA methyltransferase gene DNMT3B. SPRY3 X- and Y-inactivation is associated with a differential enrichment of repressive histone modifications and the recruitment of Polycomb 2 group proteins compared to the active X allele. Another major factor in SPRY3 repression is late replication; the inactive X and Y alleles of SPRY3 have delayed replication relative to the active X allele, even in ICF syndrome cells where the closely linked SYBL1 gene is reactivated and advanced in replication. The relatively stable maintenance of SPRY3 silencing compared with SYBL1 suggests that genes without CpG islands may be less prone to reactivation than previously thought and that genes with CpG islands require promoter methylation as an additional layer of repression.

Impact of hyperthyroidism and its correction on vascular reactivity in humans.

BACKGROUND: Although thyroid hormone (TH) exerts relevant effects on the cardiovascular system, it is unknown whether TH also regulates vascular reactivity in humans. Methods and Results- We studied 8 patients with hyperthyroidism, basally (H) and 6 months after euthyroidism was restored by methimazole (EU). Thirteen healthy subjects served as control subjects (C). We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial graded infusion of acetylcholine, sodium nitroprusside (SNP), norepinephrine, and L-NMMA (inhibitor of NO synthesis). Basal FBF (in mL. dL(-1). min(-1)) was markedly higher in H than in C (5.8+/-1.2 and 1.9+/-0.1, respectively; P<0.001) and was close to normal in EU (2.6+/-0.3, P<0.01 versus H). During acetylcholine infusion, FBF increased much more in H (+33+/-5) than in C (+14+/-3, P<0.01 versus H) and in EU (+20+/-5, P=0.01 versus H and P=NS versus C). In contrast, the response to SNP infusion was comparable in the patients and control subjects. During norepinephrine infusion, the fall in FBF was much more pronounced in H (-6+/-1) than in C (-0.7+/-0.3, P<0.005 versus H) and in EU (-1.5+/-0.3, P<0.01 versus H). Finally, inhibition of NO synthesis by L-NMMA decreased FBF by 2.8+/-0.6, 0.61+/-0.7, and 1.4+/-0.3 in H, C, and EU, respectively (H versus C and EU, P<0.05). CONCLUSIONS: In hyperthyroidism, (1) the marked basal vasodilation is largely accounted for by excessive endothelial NO production, (2) vascular reactivity is exaggerated because of enhanced sensitivity of the endothelial component, (3) the vasoconstrictory response to norepinephrine is potentiated, and (4) this abnormal vascular profile is corrected when euthyroidism is restored by medical therapy. The data demonstrate that vascular endothelium is a specific target of TH.

Mandibular metastatic hepatocellular carcinoma: report of a case involving severe and uncontrollable hemorrhage.

Hepatocellular carcinoma (HCC) is a malignant tumor with a marked tendency to spread through the portal system. Metastases from HCC usually involve lungs, surrenal glands, the skeletal and gastroenteric systems, spleen, heart and kidneys. Secondary localizations to the mandible are rare. Generally, bone metastases from HCC appear as osteolytic lesions more likely localized to the ribs, spine, femor, omer, sternum, and then to the mandible. Mandibular metastatic HCC is hemorrhagic in nature because of its hypervascularity. Any diagnostic maneuver that could end in bleeding should be avoided. Non-invasive diagnostic procedures such as computer tomography (CT) scan should be preferred. Among the invasive diagnostic procedures, only fine needle biopsy should be attempted and palliative radiotherapy could be useful for the control of local symptoms. A case report of a hemorrhagic mandibular metastatic HCC that had to be treated surgically, in order to control the severe and profuse bleeding, is presented.

Abnormal vascular reactivity in growth hormone deficiency.

BACKGROUND: The reason why patients with growth hormone (GH) deficiency (GHD) are at increased risk for premature cardiovascular death is still unclear. Although a variety of vascular risk factors have been identified in GHD, little is known regarding vascular reactivity and its contribution to premature arteriosclerosis. METHODS AND RESULTS: We assessed vascular function in 7 childhood-onset, GH-deficient nontreated patients (age 22+/-3 years, body mass index [BMI] 25+/-1 kg/m(2)) and 10 healthy subjects (age 24+/-0.4 years, BMI 22+/-1 kg/m(2)) by using strain gauge plethysmography to measure forearm blood flow in response to vasodilatory agents. The increase in forearm blood flow to intrabrachial infusion of the endothelium-dependent vasodilator acetylcholine was significantly lower in GH-deficient nontreated patients than in control subjects (P:<0.05). Likewise, forearm release of nitrite and cGMP during acetylcholine stimulation was reduced in GH-deficient nontreated patients (P:<0.05 and P:<0.002 versus controls). The response to the endothelium-independent vasodilator sodium nitroprusside was also markedly blunted in GH-deficient patients compared with control subjects (P:<0.005). To confirm that abnormal vascular reactivity was due to GHD, we also studied 8 patients with childhood-onset GHD (age 31+/-2 years, BMI 24+/-1 kg/m(2)) who were receiving stable GH replacement therapy. In these patients, the response to both endothelium-dependent and -independent vasodilators, as well as forearm nitrite and cGMP, release was not different from that observed in normal subjects. Peak hyperemic response to 5-minute forearm ischemia was significantly reduced in GH-deficient nontreated patients (17.2+/-2.6 mL x dL(-1) x min(-1), P:<0.01) but not in GH-treated patients (24.8+/-3.3 mL x dL(-1) x min(-1)) compared with normal subjects (29.5+/-3.2 mL x dL(-1) x min(-1)). CONCLUSIONS: The data support the concept that GH plays an important role in the maintenance of a normal vascular function in humans.

[Infective endocarditis: a retrospective analysis of inpatient cases]. / Endocardite infettiva: analisi retrospettiva di una casistica ospedaliera.

The authors analysed retrospectively the clinical and laboratory features of patients hospitalised in a unit of infectious diseases in the period from 1996-99. In particular, the etiology, the antimicrobial susceptibility of responsible microorganisms, criteria utilized for diagnosis, antibiotic courses and outcomes were evaluated and discussed. Echocardiography is an essential tool in the diagnosis. Infective endocarditis remains a serious infection and is still associated with high morbidity and mortality rate, despite appropriate treatment. Seriously ill patients may require prompt surgery.