Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.

Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.7 years; range 24.1-40.9 years). The HL survivors were compared with 83 age- and gender-matched healthy volunteers. The HL survivors showed unfavorable lipid profiles compared to those of healthy controls: triglycerides (p=0.01), total cholesterol (p=0.0004), low density lipoprotein cholesterol (p=0.005). In HL survivors, we found a higher prevalence of hypertension (p=0.004) and insulin resistance - HOMA-IR (p=0.0002). Ultrasonographic examination of both common carotid arteries revealed a higher prevalence of atherosclerotic plaques (p=0.0009) and higher carotid intima-media thickness (p<0.0001) in HL survivors. Markers of oxidative stress (advanced oxidation protein products, oxidized low-density lipoprotein), inflammation (hs-CRP) and endothelial dysfunction (E-selectin, PAI-1) were also higher in HL survivors (p<0.0001, p=0.0002, p=0.0031, p=0.0087, p=0.004, respectively). Adult survivors of Hodgkin lymphoma during childhood and adolescence need closer follow-up with screening of metabolic syndrome components, unfavorable lifestyle factors and early management of these risk factors.

Paediatric onset of multiple sclerosis: Analysis of chemokine and cytokine levels in the context of the early clinical course.

BACKGROUND: Inflammatory activity in children with paediatric onset multiple sclerosis (POMS) is higher than that in adults with MS. Chemokine/cytokine profiling in children may provide new insights into the disease pathogenesis and clinical course. The levels of chemokines/cytokines and their roles in POMS remain largely unknown. OBJECTIVE: To identify the possible utility of chemokines/cytokines in children with POMS, we analysed their levels at the time of disease diagnosis and in the context of subsequent clinical relapse. METHODS: CC and CXC motif ligand chemokines (CCL2, CXCL8, CXCL10, and CXCL13), interleukin (IL)-4, IL-17A, interferon gamma and B cell-activating factor in the blood and cerebrospinal fluid (CSF) of 34 POMS patients and 20 age-related controls were measured using Luminex multiplex bead and enzyme-linked immunosorbent assay techniques. Nonparametric tests were used for statistical analyses. RESULTS: The CSF levels of CXCL8 (p = 0.002), CXCL10 (p = 0.001), and CXCL13 (p<0.0001) were higher in POMS than in controls; CXCL10 and CXCL13 correlated with pleocytosis and oligoclonal bands. A subsequent clinical relapse occurred in 17/34 of the children; the median time from the diagnosis of POMS was 6 months (range, 2-64 months). The follow-up period of patients who did not experience a clinical relapse was significantly longer than the time to first relapse (p = 0.003). The initial CCL2 level was lower in relapsing than in non-relapsing patients (p = 0.063) and correlated negatively with the CSF/serum albumin ratio and positively with the time to relapse (p<0.04). CONCLUSIONS: Elevated CSF levels of CXL10 and CXCL13 in children with POMS at the time of disease diagnosis reflect inflammatory activity and suggest the involvement of adaptive immunity; elevated CXCL8 levels further indicate the involvement of innate immunity. An initial low CSF level of CCL2 may be associated with an unfavourable early MS course.

Seizure threshold manipulation in electroconvulsive therapy via repetitive transcranial magnetic stimulation. A novel way of augmentation?

INTRODUCTION: A high seizure threshold (ST) is an impeding factor in certain patients, potentially preventing a successful electroconvulsive therapy (ECT) treatment. Several pharmacological and non-pharmacological methods have been put forward to augment ECT in such patients, however, to this date, only a handful of case reports existed about the potential role of repetitive transcranial magnetic stimulation (rTMS), as an augmentation method. OBJECTIVES: and Methods: In this randomized, double-blinded, sham controlled study, we set out to test the hypothesis of whether the application of high frequency transcranial magnetic stimulation (HF rTMS) lowers the seizure threshold for electroconvulsive therapy and whether it has an effect on other aspects of ECT treatment, such as seizure duration (SD), efficacy and safety. RESULTS: 46 patients treated for a major depressive episode, indicated for ECT, were recruited to this study. A significantly lower seizure threshold was observed in the experimental group during ECT titration, on average a decrease by 34.55%, from 34.23 mC to 22.4 mC, p < 0.001 (Wilcox test). We had not observed a significant effect of TMS stimulation before ECT on seizure duration or clinical outcome. Another potentially important observation of this study is that 4 patients in the experimental group developed transient symptoms of hypomania/mania, all of which were stabilized after the combined stimulation protocol was halted spontaneously within a week, without the need to administer mood stabilizers. CONCLUSION: It is likely that HF rTMS stimulation prior to ECT is a novel and simple way of reducing the ST, which is useful in certain groups of patients undergoing this important treatment modality.

Analysis of expression profiles of genes involved in F(o)F(1)-ATP synthase biogenesis during perinatal development in rat liver and skeletal muscle.

During the process of intra-uterine mammalian fetal development, the oxygen supply in growing fetus is low. A rapid switch from glycolysis-based metabolism to oxidative phosphorylation (OXPHOS) must proceed during early postnatal adaptation to extra-uterine conditions. Mitochondrial biogenesis and mammalian mitochondrial F(o)F(1)-ATP synthase assembly (complex V, EC 3.6.3.14, ATPase) are complex processes regulated by multiple transcription regulators and assembly factors. Using RNA expression analysis of rat liver and skeletal tissue (Rattus norvegicus, Berkenhout, 1769), we describe the expression profiles of 20 genes involved in mitochondrial maturation and ATP synthase biogenesis in detail between the 16th and 22nd day of gestation and the first 4 days of life. We observed that the most important expression shift occurred in the liver between the 20th and 22nd day of gestation, indicating that the fetus prepares for birth about two days before parturition. The detailed mechanism regulating the perinatal adaptation process is not yet known. Deeper insights in perinatal physiological development will help to assess mitochondrial dysfunction in the broader context of cell metabolism in preterm newborns or neonates with poor adaptation to extra-uterine life.

Ultrasonography of blood during stasis and coagulation.

A series of in vitro and animal experiments were performed to determine ultrasonic features of blood during stasis and coagulation. Liquid whole blood became echogenic within a few seconds to 3 minutes following the onset of stasis. This occurred in citrated human blood allowed to stand and in occluded segments of vena cava and aorta of dogs. Mechanical agitation of the blood in stasis caused a disappearance of echoes. This echogenicity occurred with gray-scale and real-time ultrasonography using 7.5-mHz transducers, but was not observed with 3.5-mHz transducer used in real-time scanning. Whole blood clot was echogenic both with 7.5- and 3.5-mHz scanning. Fibrin clot was sonolucent. Echogenicity with stasis did not occur with plasma, serum, or packed erythrocytes. The development of echogenicity required the presence of fibrinogen or its products plus erythrocytes. The echogenicity of blood during stasis detectable by high-frequency ultrasonography probably was related to physical layering of blood products. The disappearance of reflective echoes following agitation suggested that the layering could be readily disrupted.

Computed air myelography of the lumbosacral spine.

Plain computed tomography (CT) of the lumbosacral spine may be a reliable method for diagnosing herniated disk when abundant epidural fat is present. When epidural fat is not sufficient, CT after the administration of nonionic contrast medium (170 mg I/ml) and/or regular metrizamide myelography have been used. Ten patients were studied by CT enhanced with air injected as a negative contrast agent. The findings were correlated with plain and contrast-enhanced (metrizamide) CT as well as conventional myelography. The technique is described and advantages and disadvantages of the method are discussed. Air-contrast CT is useful in the evaluation of herniated disk in cases with equivocal findings on plain CT and in patients with a history of allergic reaction to iodinated contrast media.

CT in the evaluation of the orbit and the bony interorbital distance.

The distance between the orbits and their individual dimensions are important in the diagnosis of craniofacial anomalies. Most observers rely on standard radiographs for measuring the bony interorbital distance. Tomography of the skull base and orbital computed tomography (CT) can also be used. This article describes the normal range of the bony interorbital distance and other useful orbital linear and angular measurements as determined from a series of CT scans of the orbits in 400 adults who had CT for other purposes. The normal interorbital distance measured at the posterior border of the frontal processes of the maxilla on nonrotated scans, in the plane of the optic nerve, ranges from 2.29 to 3.21 cm (average, 2.67 cm) in men and 2.29 to 3.20 cm (average, 2.56 cm) in women. The widest interorbital distance lies behind the posterior poles of the globes. This ranges from 3.16 to 4.10 cm (average, 3.37 cm) in men and 2.93 to 3.67 cm (average, 3.20 cm) in women.

Orbital space-occupying lesions: role of computed tomography and magnetic resonance imaging. An analysis of 145 cases.

CT and MRI of the orbit have significantly enhanced the diagnosis of orbital lesions. Because of these techniques, disorders of the globe, structures within the bony orbit, surrounding structures of the eye, and optic pathways can now be diagnosed with much more certainty than before.

CT in the evaluation of the vestibulocochlear nerves and their central pathways. Evaluation of neurotologic disorders.

CT has evolved to become an important technique for the diagnosis of neurotologic disorders. By obtaining thin sections, the central pathway of the vestibulocochlear nerve can be rather properly evaluated with satisfactory clinical correlation when pathology exists. The validity of central vestibular and audiometric signs can be best substantiated with CT. The functional neuroanatomy of the vestibulocochlear and vestibulo-oculomotor systems is discussed. Results of the assessment of endocranial lesions involving the vestibulocochlear system are presented.

Umbilical portogram in a case of Schistosomiasis japonicum.

The life cycle of shistosomes in their human host contributes to protean pathologic changes in many organs. One of these, pre-sinusoidal hepatic fibrosis in the case of S. Japonicum, was studied by an umbilical portogram during the work-up before haemofiltration. Intrahepatic portal block, with rapid tapering and marked tortuosity of portal branches as well as a very inhomogeneous and variable parenchymal pahse with poorly marginated underperfused areas and reversal of extrahepatic portal flow, was demonstrated.

Mycobacterium bovis infection in baboons (Papio papio).

Two tuberculin-positive baboons in a primate colony were found to have grossly visible tuberculous lesions in the liver, spleen, lung, and mediastinal lymph nodes on necropsy. Results of histopathologic examination of the tissues showed granulomas with Langhans giant cells. An acid-fast organism was isolated from tissues of each baboon; the isolates were identified as Mycobacterium bovis by being negative for niacin production and nitrate reduction and by their susceptibility to thiophen-2-carbosylic acid hydrazide and to 5% glycerol.

Magnetic resonance imaging in the diagnosis of nonsquamous tumors of the head and neck.

Nonsquamous cell tumors of the head and neck can be reliably evaluated by MRI. In certain pathologic entities, it appears that MRI can provide more information than CT scan.

Ultrasonically guided percutaneous aspiration of lymphoceles following renal transplantation: a diagnostic and therapeutic method.

Percutaneous aspirations of perirenal collections under ultrasonographic control is a safe and simple therapeutic and diagnostic procedure in patients who have developed lymphoceles after renal transplantation. The diagnostic and therapeutic yield is far superior to any other method, short of surgical exploration. We encountered no complications in our cases. The technique is described in detail.

Percutaneous biopsy of renal transplants using ultrasonographic guidance.

The transplanted kidney is an ideal organ for study by ultrasonic methods because it is located superficially in the iliac fossa and it is free of superimposed echoes from the intestines. Therefore, it is possible to localize the transplant accurately, measure the distance from the skin to the surface of the kidney and determine with precision the angle of the intended pathway of the needle.