Patterns of drug resistance among patients with tuberculous pleural effusion in Greece.

SETTING: Data on the relationship between pleural tuberculosis (TB) and anti-tuberculosis drug resistance are scarce. OBJECTIVE: To determine the patterns of drug resistance among pleural Mycobacterium tuberculosis isolates in Greece and the incidence of tuberculous pleural effusion (TPE) among patients with multidrug-resistant (MDR) or extensively drug-resistant (XDR) pulmonary TB. DESIGN: Drug susceptibility testing (DST) results recorded in the database of the National Reference Centre for Tuberculosis in Athens, Greece, over a 9-year period (2003-2011) were reviewed. Chest X-rays from hospitalised patients with pulmonary MDR/XDR-TB during the same period were also reviewed for the presence of TPE. RESULTS: Resistance to at least one first-line drug was observed in 11% of the cases (MDR-TB 3%, XDR-TB 1%), while 29% of the patients with pulmonary MDR/XDR-TB presented with TPE during the course of their disease, the majority ipsilateral to the lung lesions, which responded to guided anti-tuberculosis treatment. CONCLUSION: The prevalence of drug resistance among pleural M. tuberculosis isolates in Greece highlights the importance of DST prior to treatment selection in TPE patients. In our study population, TPE that developed in one third of the patients with pulmonary MDR/XDR-TB usually resolved with DST-guided anti-tuberculosis treatment.

The gymnasts' hip and groin: a magnetic resonance imaging study in asymptomatic elite athletes.

OBJECTIVE: Specific patterns of developmental adaptation of the proximal femur have been recognized in some sports. Gymnastics are characterized by repetitive axial loading and hip rotations in combination with extreme hip positions. It is unknown how and if these forces can affect an immature skeleton in the long term. We sought to evaluate this, by means of magnetic resonance imaging of the hip and groin of such elite asymptomatic athletes. MATERIALS AND METHODS: We performed a case-control comparative MR imaging study of both hips and groin of 12 (7 male, 5 female) skeletally mature young (mean age 18.6 years) asymptomatic international level gymnasts with a minimum of 10 years' training with age-matched non-athletes. At the time of recruitment, none of the athletes had a recorded musculoskeletal complaint or injury in the anatomical area around the hip. RESULTS: The study showed that elite gymnasts share four common morphological characteristics on MRI that deviate from normal and are considered to be the result of adaptational changes to the specific sport: high centre-column-diaphysis angle (coxa valga140° on average), ligamentum teres hypertrophy, friction of the iliotibial band with oedema surrounding the greater trochanter, and a high incidence (62.5 %) of radiological appearances of ischiofemoral impingement. CONCLUSION: Our study showed that elite gymnasts share four common morphological characteristics on MRI that deviate from normal. These findings were in asymptomatic subjects; hence, radiologists and sports physicians should be aware of them in order to avoid unnecessary treatment.

The role of hip arthroscopy in the management of osteonecrosis.

Hip arthroscopy has emerged as a diagnostic and therapeutic tool in the management of osteonecrosis (ON) of the femoral head. Direct visualization of the joint, aids the staging of the disease, while mechanical symptoms and pain can be alleviated by addressing the often coexisting intra-articular pathology (labral tears, chondral delamination, loose bodies and synovitis) thereby improving the clinical outcome in some patients. The article explores the role and possible value of hip arthroscopy as a surgical technique in the treatment of hip ON.

Complications of arthroscopic surgery of the hip.

Over recent years hip arthroscopic surgery has evolved into one of the most rapidly expanding fields in orthopaedic surgery. Complications are largely transient and incidences between 0.5% and 6.4% have been reported. However, major complications can and do occur. This article analyses the reported complications and makes recommendations based on the literature review and personal experience on how to minimise them.

Efficacy and tolerability of oral lacosamide as adjunctive therapy in pediatric patients with pharmacoresistant focal epilepsy.

The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range=3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings.

Quality of life in different age groups after metal-on-metal hip resurfacing arthroplasty.

Hip resurfacing arthroplasty is known to improve quality of life (QoL) and allow increased activity levels in young patients. It is, however, traditionally offered to the younger age group of patients, largely those aged under 60 years. We studied 42 consecutive patients (42 hips) aged 60 years or over (mean age 64) and 41 consecutive patients (42 hips) under this age (mean age 49), all of whom had undergone a metal-on-metal hip resurfacing arthroplasty. A modified Harris hip score was translated to QoL scores using the Rosser Index Matrix immediately pre-operatively, and at six weeks, six months, one year and four years after surgery. We found a significant improvement in QoL for both groups (p <0.0001) but no difference between the two groups. The maximum improvement was reached one year after surgery. Implant survival at four years was also similar (97.6% for group I and 100% for group II). We thus conclude that in carefully selected active patients aged 60 years and over, hip resurfacing arthroplasty provides significant and equal QoL improvement as it does for those under this age with similar implant survival. For this reason, age alone should not influence a surgeon's decision to proceed with a hip resurfacing arthroplasty.

Reliability of Greek version Gross Motor Function Classification System.

The Gross Motor Function Classification System for Cerebral Palsy (GMFCS), a reliable and valid system, has been widely utilized for objective classification of the patterns of motor disability in children with cerebral palsy. The objective of this study was to produce a Greek version of the instrument, with the same construct as the original one and to investigate the reliability of application of the Greek version GMFCS. Translation and back translation was made by two of the authors, one of whom did not know the original English text. The final translation was fixed by consensus. Two physicians were trained and given practice in the use of the GMFCS and its application to clinical documentation. The raters classified children with cerebral palsy according to GMFCS - Greek version. The reliability was assessed with the weighted kappa statistic. The sample consisted of 47 boys and 47 girls, mean age 5.4 years. The overall weighted Kappa was 0.80 (95% CI=0.67-0.94). Weighted Kappa for level I was 0.91 (95% CI=0.74-1.09), for level II, 0.78 (95% CI=0.62-0.95), for level III, 0.85 (95% CI=0.68-1.02), for level IV, 0.85 (95% CI=0.67-1.03) and for level V, 0.84 (95% CI=0.66-1.03). The inter-rater reliability was lowest at level II. Percent agreement was 75%. Results of this study suggest that GMFCS - Greek version can be used reliably to classify patients with CP from clinical documentation. These results further support use of the GMFCS in clinical settings and for research. Investigation is needed to further assess the reliability and to determine the validity of the Greek version of the GMFCS.

Infection in knee replacements after previous injection of intra-articular steroid.

We reviewed 231 patients who had undergone total knee replacement with an AGC (Biomet) implant over a period of 2.5 years. After applying exclusion criteria and with some loss to follow-up, there were 144 patients available for study. These were divided into two groups; those who had received intra-articular steroid in the 11 months before surgery and those who had not. There were three deep infections, all of which occurred in patients who had received a steroid injection. The incidence of superficial infection was not significantly different in the two groups. Five patients had undergone investigation for suspected deep infection because of persistent swelling or pain and all of these had received an intra-articular injection pre-operatively. We conclude that the decision to administer intra-articular steroids to a patient who may be a candidate for total knee replacement should not be taken lightly because of a risk of post-operative deep infection.

Knowledge and attitude of the Greek educational community toward epilepsy and the epileptic student.

The purpose of this study was to investigate primary and secondary school teachers' knowledge of and attitudes toward epilepsy and the epileptic child. A 14-item questionnaire was administered to 300 teachers in three major Greek cities. The focus of interest was the teachers' basic knowledge of epilepsy, their perceptions of the consequences of epilepsy on a student's academic potential and behavior, their tendency to accept or reject the epileptic child, and their ability to help a convulsing child. The majority of teachers have a correct opinion about the nature of epilepsy and its short-term prognosis (control by medication), but are very pessimistic about its long-term prognosis (cure). They believe that although some epileptic children may have mental, learning, or behavioral problems, most of then do not and are therefore capable of academic achievements. The attitude of most teachers is very positive toward the epileptic child, and almost all believe that these children should continue their studies at their regular school. An alarming finding is the reported inability of most teachers to help a convulsing child. Personal knowledge of an epileptic student was a significant factor in determining many of the teachers' responses. Better education of teachers concerning epilepsy and the practical skills involved in first-aid are necessary measures for Greek teachers.

Written language skills in children with benign childhood epilepsy with centrotemporal spikes.

PURPOSE: The goal of this work was to study written language skills in children with benign childhood epilepsy with centrotemporal spikes (BCECTS) in the absence of atypical clinical or electroencephalographic (EEG) features (n = 32), as compared with controls (n = 36). METHODS: BCECTS patients (7-16 years), attending regular school, without cognitive or behavioral regression, or atypical EEG patterns, completed four tests assessing written language skills and one nonverbal cognitive test. School performance information was recorded. Seizure types, duration, and frequency; awake and sleep interictal EEG findings; and medication status were documented. Epilepsy and educational outcome was recorded for a period of 1-5 years after diagnosis. RESULTS: As a group, BCECTS patients performed significantly worse than controls in spelling, reading aloud, and reading comprehension; presented dyslexic-type errors; and frequently had below-average school performance. Among 11 with poor written language performance, 4 had developmental dysfunctions before school and seizure onset and, as a group, demonstrated low performance on a nonverbal cognitive test. Even though 65.6% were on anticonvulsants due to frequent seizures and/or seizures while awake, none belonged to the atypical BCECTS spectrum with respect to clinical or EEG findings. Increased epilepsy duration and seizure frequency were less represented in patients with no or mild written language problems than in those with poor performance. Otherwise, clinical course and EEG findings in this group were no different than those for the 11 children with severe written language problems. Clinical follow-up indicated that learning problems appear persistent and several children require remedial classes and/or tutoring after the epilepsy has resolved. CONCLUSIONS: Children with severe but not atypical BCECTS performed, as a group, significantly worse than controls in written language skills, specifically in spelling, reading, aloud and reading comprehension; they also presented many difficulties also found in children with dyslexia. However, poor written language performance was not considered specific to BCECTS because it occurred in children with generally low cognitive capacity and/or preexisting developmental dysfunctions. Moreover, a dissociation between epilepsy outcome and learning problem outcome, in the subgroup with poor performance, casts doubt on the existence of a possible causal link between BCECTS and educational performance.

Psychogenic status epilepticus in children.

Epilepsy features, psychiatric profile, psychosocial factors, and outcome are described for six children (three males) aged 5-15 years (mean 12.1) with psychogenic status epilepticus (PSE), i.e., prolonged or repetitive psychogenic seizures (PSs), >30 minutes, simulating status epilepticus. They had epilepsy, they were on chronic anticonvulsants (ACVs), and some had other neurological deficits. All received intravenous and/or rectal ACVs prior to suspicion of PSE. PSE was confirmed via video/EEG, demonstrating no epileptogenic activity during alleged seizures. Provocation and placebo therapy techniques were used in two. Psychiatric assessment identified comorbid disorders such as depression, anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, and posttraumatic stress disorder. Psychosocial stressors were almost ubiquitous. Psychiatric intervention included psychotherapy, family therapy, and medical treatment in one patient. Outcome was monitored for an average of 3.6 years (3-5 years). PSE did not recur. PSs recurred in three. Psychiatric comorbidity improved in four, who accepted psychiatric intervention and whose epilepsy also improved. In conclusion, the occurrence of PSE in children and adolescents with epilepsy is stressed. Prompt diagnosis was often missed in the acute care setting, and this carries important implications for iatrogenic complications. PSE diagnosis resulted in identification and management of comorbid psychiatric disorders. This was probably important in reducing the predominating anxiety and affective disorders in most patients as well as PSE recurrence. Epilepsy severity and associated deficits were most likely important factors in determining outcome.

Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with oral diltiazem and limited intensive care management.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) patients are frequently treated with prophylactic nimodipine and undergo invasive monitoring of blood pressure and volume status in an intensive care unit (ICU) setting to decrease the incidence of delayed ischemic neurological deficit (DIND) and improve functional outcomes. The goal of this study was to examine the incidence of DIND and poor functional outcomes in a consecutive series of SAH patients treated with a different regimen of prophylactic oral diltiazem and limited use of intensive care monitoring. METHODS: The study involved a consecutive series of 123 aneurysmal SAH patients treated by the senior author who were admitted within 72 hours of hemorrhage and who never received nimodipine or nicardipine. Functional outcomes were graded using the Glasgow Outcome Scale (GOS). RESULTS: Of the 123 patients identified, favorable outcomes (GOS 4 and 5) were achieved in 74.8%. The incidence of DIND was 19.5%. Hypertensive, hypervolemic, hemodilutional (HHH) therapy was used in 10 patients (8.1%) and no patients were treated for DIND by endovascular means. Seven patients (5.7%) had a poor functional outcome or death because of DIND and two of these were related to complications of HHH therapy. These results were compared to contemporary series of SAH patients managed with other treatment protocols. CONCLUSIONS: Functional outcomes of patients treated with a regimen of oral diltiazem, limited use of ICU monitoring and HHH therapy for DIND compare favorably with other contemporary series of SAH patients.

Neurometabolic testing in developmental delay.

The goal of this study was to examine the usefulness of neurometabolic testing in patients with unexplained developmental delay. We included 118 patients from ages 3 months to 13 years. The evaluation was conducted according to a protocol that called for stepwise investigations with the intention to minimize unnecessary tests. Clinical and neuroradiologic abnormalities were used as guidelines for the type and extent of the neurometabolic work-up. Based on our results, a diagnosis for a neurometabolic disorder was established in 16 patients (13.6%). Findings regarding abnormal metabolites (amino acids, ammonia, lactate, pyruvate, urine organic acids) did not lead to a diagnosis but to further investigations. Abnormalities in lysosomal enzymes, very-long-chain fatty acids, and urine mucopolysaccharides were definitive in establishing a diagnosis. In conclusion, in children with slowly progressing development with no apparent cause, there is a need for guidelines regarding the type of patients who need to be tested and the kind and extent of neurometabolic diagnostic work-up.

Clinical outcomes after carotid endarterectomy: comparison of the use of regional and general anesthetics.

OBJECT: The authors analyzed their series of carotid endarterectomies (CEAs), which were performed after administration of either a general or regional anesthetic, to determine whether the choice of anesthetic affected patients' clinical outcomes and length of hospital stay. METHODS: A series of 803 consecutive CEAs performed between July 1990 and February 1999 was reviewed. Cases were analyzed for patient demographics, comorbid medical states, and perioperative complications. Contingency-table statistical analysis was used to compare the incidence of comorbid medical states and perioperative complications between patients who underwent CEA in which either a regional or general anesthetic was used. Student's t-test was used to compare the length of hospital stay and mean patient age. A regional anesthetic was used for 632 CEAs, and a general anesthetic was used for 171 operations. There were no statistically significant intergroup differences in demographics or comorbid medical states. The incidence of perioperative stroke and death did not differ significantly between the regional (2.7%) and the general anesthetic groups (2.3%). However, the incidence of nonneurological, nonfatal complications was significantly less in the regional anesthetic (1.6%) than in the general anesthetic group (14.6%, p<0.0001). Patients undergoing CEA in which a regional anesthetic was used had a significantly lower incidence of cardiopulmonary complications (myocardial infarction and postoperative intubation), cervical complications (neck hematomas and cranial nerve injuries), and urological complications (urinary retention) than patients who underwent surgery after receiving a general anesthetic. CONCLUSIONS: Patients undergoing CEA in which a regional anesthetic was used had significantly fewer nonneurological, nonfatal complications, particularly cardiopulmonary complications, than similar patients surgically treated after induction of general anesthesia.

Paracrine regulation of colony-stimulating factor-1 in medulloblastoma: implications for pathogenesis and therapeutic interventions.

OBJECTIVE: Colony-stimulating factor (CSF)-1, a chemotactic and mitogenic factor for macrophages and microglia, is expressed in a variety of nervous system tumors and when present in nonneural malignancies, is associated with marked inflammatory infiltrates, dissemination, and poorer prognosis. This study investigated the paracrine effects of CSF-1 production by medulloblastoma cells on the macrophage/microglial lineage. METHODS: A recurrent metastatic desmoplastic medulloblastoma was isolated from a 26-year-old man and propagated in tissue culture. Cellular phenotype and proliferation were assessed by immunocytochemical techniques; transcript expression for CSF-1, granulocyte macrophage-CSF, interleukin-3, and c-fms (the receptor for CSF-1) was examined with reverse transcriptase-polymerase chain reaction; and conditioned media and coculture paradigms were used to study cytokine effects on cellular proliferation. RESULTS: Serially passaged cells were uniformly immunoreactive for two lineage-independent neuroepithelial markers, nestin and vimentin. A subpopulation of cells with morphological characteristics of early differentiation stained for neurofilament 66 (7%) and microtubule-associated protein (5%) (markers of early neuronal precursors and postmitotic neurons, respectively) and for the Yp subunit of glutathione-S-transferase (3%) (a marker of early oligodendroglial progenitors). Tumor cells expressed transcripts for CSF-1, but not for granulocyte macrophage-CSF, interleukin-3, or c-fms. Treatment of microglia with serum-free medulloblastoma-conditioned media significantly increased proliferation (P < 0.001), suggesting the secretion of CSF-1. Coculture of medulloblastoma cells and microglia significantly increased proliferation of both cell types (each condition, P < 0.01). CONCLUSION: These observations suggest that CSF-1 mediates important paracrine interactions between transformed cells and the immune system, resulting in increased growth rate and metastatic potential. Future therapeutic goals need to include immunotherapeutic protocols to modulate this interaction.

Bone morphogenetic proteins induce astroglial differentiation of oligodendroglial-astroglial progenitor cells.

We have used bipotent postnatal cortical oligodendroglial-astroglial progenitor cells (O-2As) to examine the role of inductive signals in astroglial lineage commitment. O-2A progenitor cells undergo progressive oligodendroglial differentiation when cultured in serum-free medium, but differentiate into astrocytes in medium supplemented with FBS. We now report that the bone morphogenetic proteins (BMPs), a major subclass of the transforming growth factor beta (TGFbeta) superfamily, promote the selective, dose-dependent differentiation of O-2As into astrocytes with concurrent suppression of oligodendroglial differentiation. This astroglial-inductive action is not sanctioned by other members of the TGFbeta superfamily. Astroglial differentiation requires only very brief initial exposure to the BMPs and is accompanied by increased cellular survival and accelerated exit from cell cycle. Dual-label immunofluorescence microscopy documents that O-2A progenitor cells express a complement of BMP type I and type II receptor subunits required for signal transduction. Furthermore, expression of BMP2 in vivo reaches maximal levels during the period of gliogenesis. These results suggest that the BMPs act as potent inductive factors in postnatal glial lineage commitment that initiate a stable program of astroglial differentiation.

Microglial lineage species are expressed in mammalian epidermal growth factor-generated embryonic neurospheres.

The epigenetic signals and progenitor cell species involved in progressive neural maturation in the mammalian brain are poorly understood. Although these complex developmental issues can be examined in cultures of generative zone progenitor cells, analysis of signaling relationships in complex progenitor cell systems requires the meticulous definition of the cellular complement at each developmental stage. The presence of microglia within the generative zone cultures would further complicate these developmental analyses. Utilizing the microglial markers Griffonia simplicifolia B4 isolectin, carbocyanine dye-acetylated low density lipoprotein, F4/80, and Mac-1 we now report the presence of microglia within cultures of late embryonic murine epidermal growth factor-derived generative zone progenitor cells. Cytokine treatment of serially passaged epidermal growth factor-generated neurospheres altered the phenotype of the microglia in culture. Macrophage colony-stimulating factor treatment promoted the expression of spindle-shaped microglia, whereas granulocytemacrophage colony-stimulating factor treatment promoted the elaboration of flat and amoeboid microglia. Treatment with microglial-conditioned medium or 10% non-heat inactivated fetal calf serum led to an increased complement of both phenotypes. Microglia could be generated from single isolated neurospheres, and there were differences in the number of microglial lineage species obtained from distinct oligopotent progenitor cells, raising the possibility that a complement of this cellular lineage may be derived from a progenitor cell present within the generative zones. These observations indicate that microglia are present within the generative zone progenitor cell system, and this system thus represents an important experimental resource to examine the progenitor cell maturation and the origin of the microglial lineage.

Cytokines regulate the cellular phenotype of developing neural lineage species.

The patterns and mechanisms of action of inductive signals that orchestrate neural lineage commitment and differentiation in the mammalian brain are incompletely understood. To examine these developmental issues, we have utilized several culture systems including conditionally immortalized cell lines, subventricular zone progenitor cells and primary neuronal cultures. A neural stem and progenitor cell line (MK31) was established from murine embryonic hippocampus by retroviral transduction of temperature-sensitive alleles of the simian virus 40 large tumor antigen. At the non-permissive temperature for antigen expression (39 degrees C) in serum-free media, the neural stem cells give rise to a series of increasingly mature neuronal progenitor and differentiated cellular forms under the influence of a subset of hematolymphopoietic cytokines (interleukins 5, 7, 9 and 11), when individually co-applied with transforming growth factor alpha, after pretreatment with basic fibroblast growth factor. These cellular forms elaborated a series of progressively more mature neurofilament proteins, a sequential pattern of ligand-gated channels, and inward currents and generation of action potentials with mature physiological properties. Because the factors regulating the development of central nervous system astrocytes have been so difficult to define, we have chosen to focus, in this manuscript, on the elaboration of this cell type. At 39 degrees C, application of a subfamily of bone morphogenetic proteins of the transforming growth factor beta superfamily of growth factors sanctioned the selective expression of astrocytic progenitor cells and mature astrocytes, as defined by sequential elaboration of the Yb subunit of glutathione-S-transferase and glial fibrillary acidic protein. These lineage-specific cytokine inductive relationships were verified using subventricular zone neural progenitor cells generated by the application of epidermal growth factor, alone or in combination with basic fibroblast growth factor, to dissociated cellular cultures derived from early embryonic murine brain, a normal non-transformed developmental population. Finally, application of a different series of cytokines from five distinct factor classes (basic fibroblast growth factor, platelet-derived growth factor-AA, insulin-like growth factor 1, neurotrophin 3 and representative gp130 receptor subunit-related ligands) caused the elaboration of oligodendroglial progenitor species and post-mitotic oligodendrocytes, defined by progressive morphological maturation and the expression of increasingly advanced oligodendroglial and oligodendrocyte lineage markers. In addition, seven different gp130-associated neuropoietic (ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin-M) and hematopoietic (interleukins 6, 11, 12, granulocyte-colony stimulating factor) cytokines exhibited differential trophic effects on oligodendroglial lineage maturation and factor class interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Mild de Lange syndrome--does it exist?

A pair of mildly retarded, microcephalic twins (probably identical) are reported. They were initially diagnosed as having the de Lange syndrome on the basis of the synophrys, but, on follow-up, their main intellectual defect was in the area of expressive speech. It is suggested that the evidence in the literature for the existence of so-called mild de Lange is sparse and that the twins in this report might well have a different, possibly unique condition.