Towards bedside washing of stored red blood cells: a prototype of a simple apparatus based on microscale sedimentation in normal gravity.

BACKGROUND AND OBJECTIVES: Infusion of by-products of red blood cell (RBC) storage-induced degradation as well as of the residual plasma proteins and the anticoagulant-preservative solution contained in units of stored blood serve no therapeutic purpose and may be harmful to some patients. Here, we describe a prototype of a gravity-driven system for bedside washing of stored RBCs. MATERIALS AND METHODS: Stored RBCs were diluted to 10% haematocrit (Hct) with normal saline, matching the conventional washing procedure. The dilute RBC suspensions were passed through a column of coiled tubing to allow RBC sedimentation in normal gravity, thus separating them from the washing solution. Washed RBCs were collected using bifurcations located along the tubing. Washing efficiency was quantified by measuring Hct, morphology, deformability, free haemoglobin and total-free protein. RESULTS: The gravity-driven washing system operating at 0·5 ml/min produced washed RBCs with final Hct of 36·7 ± 3·4% (32·3-41·2%, n = 10) and waste Hct of 3·4 ± 0·7% (2·4-4·3%, n = 10), while removing 80% of free haemoglobin and 90% of total-free protein. Washing improved the ability of stored RBCs to perfuse an artificial microvascular network by 20%. The efficiency of washing performed using the gravity-driven system was not significantly different than that of conventional centrifugation. CONCLUSIONS: This proof-of-concept study demonstrates the feasibility of washing stored RBCs using a simple, disposable system with efficiency comparable to that of conventional centrifugation, and thus represents a significant first step towards enabling low-cost washing of stored blood at bedside.

Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism.

The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells. Morphological analysis on neuronal cells differentiated from the KS-ASD patient-derived hiPSC clones showed significantly shorter neurites and reduced arborization compared to cells generated from healthy controls. Moreover, density of dendritic protrusions of neuronal cells derived from KS-ASD hiPSCs was lower than that of control cells. Synaptic connections and spontaneous neuronal activity measured by live cell calcium imaging could be detected after 5 weeks of differentiation, when KS-ASD cells exhibited higher sensitivity of calcium responses to acetylcholine stimulation indicating a lower nicotinic cholinergic tone at baseline condition in KS-ASD cells. In addition, gene expression profiling of differentiated neuronal cells from the KS-ASD patient revealed higher expression of proliferation-related genes and lower mRNA levels of genes involved in neuronal maturation and migration. Our data demonstrate anomalous neuronal morphology, functional activity and gene expression in KS-ASD patient-specific hiPSC-derived neuronal cultures, which offers an in vitro system that contributes to a better understanding of KS and potentially other neurodevelopmental disorders including ASD.

The importance of IgM positivity in laboratory diagnosis of gestational and congenital syphilis.

From January 1, 2009 through December 31, 2011, from 33,753 blood samples for syphilis screening, Treponema pallidum infections were confirmed in 241 pregnant women at the Department of Dermatology, Venerology, and Dermatooncology of Semmelweis University Budapest. In this period, four children born to inadequately or untreated women were confirmed to have connatal syphilis. The height of rapid plasma reagin (RPR) titer was measured to determine the stage of the infection and to examine the success of the antilues therapy. The diagnosis of maternal syphilis infection was confirmed with enzyme linked immunosorbent assay (ELISA), T. pallidum particle agglutination (TPPA), and IgG and IgM immunoblots. Maternal IgM immunoblot results identify mothers at risk of delivering babies with connatal syphilis better than the height of maternal RPR titer. The standard serological tests are less useful in newborns because of IgG transfer across the placenta. IgM test which depends on the infant's response has more specificity in diagnosing connatal syphilis.

Clinical, radiological and genetic aspects of leukodystrophies.

The authors summarize the pathomechanism of the myelination process, the clinical, radiological and the genetical aspects of the leukodystrophies, as in 18q deletion syndrome, adrenoleukodysrtophy, metachromatic leukodystrophy, Pelizaeus-Merzbacher leukodystrophy, Alexander disease and olivo-ponto-cerebellar atrophy (OPCA).

Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis.

Astroglial cells are essential components of the neurogenic niches within the central nervous system. Emerging evidence suggests that they are among the key regulators of postnatal neurogenesis. Although astrocytes have been demonstrated to possess the potential to instruct stem cells to adopt a neuronal fate, little is known about the nature of the glia-derived instructive signals. Here we propose that all-trans retinoic acid, one of the most powerful morphogenic molecules regulating neuronal cell fate commitment, may be one of the glia-derived factors directing astroglia-induced neurogenesis. According to data obtained from several complementary approaches, we show that cultured astrocytes express the key enzyme mRNAs of retinoic acid biosynthesis and actively produce all-trans retinoic acid. We show that blockage of retinoic acid signaling by the pan-RAR antagonist AGN193109 prevents glia-induced neuron formation by noncommitted stem cells. Therefore, we provide strong in vitro evidence for retinoic acid action in astroglia-induced neuronal differentiation.

Comparison of clinical symptoms and magnetic resonance angiographic (MRA) results in patients with trigeminal neuralgia and persistent idiopathic facial pain. Medium-term outcome after microvascular decompression of cases with positive MRA findings.

Neurovascular compression (NC) seems to have been confirmed as the major cause of classical trigeminal neuralgia (TN). In spite of the large number of surgically positive cases, however, there are still cases where no vascular compression of the trigeminal nerve can be found. To evaluate whether NC could be demonstrated preoperatively, high-resolution magnetic resonance angiography (MRA) was performed in 287 consecutive patients with TN and persistent idiopathic facial pain (PIFP) on a 0.5-T and a 1-T MR unit. Depending on the clinical symptoms, the TN cases were divided into typical TN and trigeminal neuralgia with non-neuralgic interparoxysmal pain (TNWIP) groups. Microvascular decompression (MVD) was performed in 103 of the MRA-positive cases. The patients were followed up postoperatively for from 1 to 10 years. The clinical symptoms were compared with the imaging results. The value of MRA was assessed on the basis of the clinical symptoms and surgical findings. The outcome of MVD was graded as excellent, good or poor. The clinical symptoms were compared with the type of vascular compression and the outcome of MVD. The MRA image was positive in 161 (56%) of the 287 cases. There were significant differences between the clinical groups: 66.5% of the typical TN group, 47.5% of the TNWIP group and 3.4% of the PIFP group were positive. The quality of the MR unit significantly determined the ratio of positive/negative MRA results. The surgical findings corresponded with the MRA images. Six patients from the MRA-negative group were operated on for selective rhizotomy and no NC was found. Venous compression of the trigeminal nerve was observed in a significantly higher proportion in the background of TNWIP than in that of typical TN on MRA imaging (24.1% and 0.8%, respectively) and also during MVD (31.2% and 1.2%, respectively). Four years following the MVD, 69% of the patients gave an excellent, 23% a good and 8% a poor result. The rate of some kind of recurrence of pain was 20% in the typical TN and 44% in TNWIP group. The rate of recurrence was 57% when pure venous compression was present. The only patient who was operated on from the PIFP group did not react to the MVD. The clinical symptoms and preoperative MRA performed by at least a 1-T MR unit furnish considerable information, which can play a role in the planning of the treatment of TN.

Familial multiple sclerosis: case study of three affected siblings.

We report on three sisters with new-onset multiple sclerosis (MS). The symptoms of the eldest sister began in 1993 with lower-limb weakness and paraesthesia. In 1998, she had limb weakness, nystagmus and ataxia. Magnetic resonance imaging (MRI) of the brain, the cerebrospinal fluid (CSF) examinations, and evoked potentials verified MS. The middle sister exhibited left-side optic neuritis in 1998. All findings pointed to MS. The third sister had subjective complaints such as paraesthesias and vertigo. MRI and CSF results supported the diagnosis. Both parents and all four grandparents are without neurological signs; the brain MRI examinations on the parents were negative. The prevalence of familial MS in first-degree relatives is 5-10%, while that in twins is 20-30%. In this case, environmental factors seem to play the crucial role. Although the anamnesis as concerns MS proved negative in the other family members examined here, further genetic examination of the sisters is needed.

Venous cerebral infarction due to simultaneous occurrence of dural arteriovenous fistula and developmental venous anomaly.

A case of a left frontal lobe infarction in a 31-year-old male patient is presented. This patient had bilateral frontal dural arteriovenous fistulae (DAVF) and a left frontal developmental venous anomaly (DVA). It is suggested that the simultaneous occurrence of these vascular anomalies was the cause of his infarction.

Donor site angiography before mandibular reconstruction with fibula free flap.

The use of fibular free flaps has become established as a reliable and popular method for reconstruction of segmental mandibular defects. The role of routine preoperative angiography remains controversial. Sixty four digital subtraction angiograms were studied in a series of 39 consecutive patients clinically judged to be satisfactory candidates for fibula free transfer. Angiographic findings revealed vascular anomalies in 10 extremities (15.6%). Regarding the high potential for significant donor site morbidity authors consider vascular imaging essential part of preoperative evaluation.

[Results of surgical treatment in hemifacial spasm--the role of MR-angiography in detecting microvascular compression]. / Hemifacialis spasmus mútéti kezelésének eredménye MR-angiográfiával kimutatott microvascularis kompresszió esetén.

The authors evaluated the follow-up results of microvascular decompression (sec. Janetta) in 8 patients with hemifacial spasm (HFS). Indication was based on there dimensional time of flight magnetic resonance angiography with 0.5T Elscint Gyrex V Dix equipment. Contrast material was administered in every case and maximum intensity projection and thin slice reconstruction were performed in three standard directions. Vascular contact with the facial nerve in the entry zone was identified on the symptomatic side in 10 patients. No contact was detected in 2 cases. Microvascular decompression was performed in 8 cases. The surgical and neuroradiological findings were identical in every cases. Five patients were completely free of HFS immediately after surgery, and another 2 patients became free of HFS during the next few weeks. Only 1 patient had uncured symptoms. In conclusion, the authors suggest that microvascular decompression of the facial nerve may evolve as the method of choice if vascular contact is proved by 3D TOF MRA.

Three-dimensional time-of-flight MR angiography in trigeminal neuralgia on a 0.5-T system.

The goal of this study was to analyze the diagnostic value of three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA), performed on a 0.5-T system in the detection of neurovascular compression in patients with trigeminal neuralgia (TN). One hundred seventy-two TN patients were examined using plain and contrast-enhanced 3D TOF MRA on a 0.5-T system. Maximum intensity projection (MIP) reconstruction was performed in three standard planes. Both the original and the reconstructed images were studied to search for vascular compression shown by close neurovascular contact and/or dislocation of the trigeminal nerve. Forty-two TN patients underwent surgical exploration of the posterior fossa. Results of MRA were compared with clinical data in all cases and to result of surgery in the surgically treated cases. Neurovascular contact at the root entry zone of the trigeminal nerve was detected on the symptomatic side in 94 patients, and on the asymptomatic side in 12 patients. Sensitivity, specificity, accuracy, as well as positive and negative predictive value of 3D TOF MRA in the detection of neurovascular compression in the patient group undergoing surgery, were 97.6, 92.5, 95.0, 93.0, and 97.4%, respectively. Three-dimensional TOF MRA performed on a 0.5-T system appears to be not less effective than similar examinations by higher field strength devices in the detection of neurovascular contact. This sequence accurately demonstrates the presence of neurovascular compression, and in this way valuable information may be achieved for the planning of surgical therapy of patients with trigeminal neuralgia.

[Donor site digital subtraction angiography before mandible reconstruction with free fibula transplantation]. / Az alsó végtag digitális szubtrakciós angiográfiája a mandibula fibulalebennyel történó rekonstrukciója elótt.

The use of fibula free flap has become established as a reliable and popular method for reconstruction of segmental mandibular defects. Vascular anomalies of the donor site may compromise the blood supply of the flap, may jeopardize perfusion of the foot or cause technical difficulties during the procedure. Clinical examination of the circulation in the lower extremities may have relatively normal results. Preoperative vascular imaging detects aberrant cases and thus may contraindicate the use of fibula free flap or may alter the surgical plan. Authors performed 64 preoperative lower-limb digital subtraction angiographies (DSA) in a series of 39 consecutive patients clinically judged to be satisfactory candidates for free fibula transfer. DSA detected vascular anomalies in 10 extremities (15.6%). Regarding the high potential for significant donor site morbidity authors consider vascular imaging essential part of preoperative evaluation.

[Surgical treatment of giant basilar artery aneurysm with induced hypothermia and circulatory arrest]. / Arteria basilaris óriásaneurysma mútéti kezelése hypothermiában végzett keringésmegállítás alatt.

Surgical management of giant and complex posterior circulation aneurysms continues to be a technically difficult task with high operative morbidity. To minimize morbidity we have used cardiopulmonary bypass and circulatory arrest for the treatment of a giant basilar aneurysm. A 48-year-old woman presented with sudden headache. Magnetic resonance angiography revealed a giant basilar aneurysm. On the 2nd hospital day she developed right sided hemiparesis and cranial nerve deficits as a result of the second rupture of the aneurysm. The aneurysm was successfully treated and no significant neurological complications were related to this technique. This initial experience indicates that patients with giant posterior circulation aneurysm that cannot be treated using conventional techniques might benefit from a surgical approach that included the use of deep hypothermic circulatory arrest.

The place of magnetic resonance and ultrasonographic examinations of the parotid gland in the diagnosis and follow-up of primary Sjögren's syndrome.

OBJECTIVE: The aim was to determine the place of magnetic resonance imaging (MRI) and ultrasonographic (US) examination in the diagnosis and follow-up of Sjögren's syndrome (SS). METHODS: Parotid MRI and US examinations were carried out on 44 primary SS patients and 52 controls of similar age. RESULTS: The most important structural changes in SS were different degrees of parenchymal inhomogeneity, which could be detected by both methods, and were found more frequently in the SS patients than in the controls (MRI: 95.4 vs 17. 3%; US: 88.6 vs 7.7%; P<0.001). There was good agreement between the MRI and US findings both in the SS cases (93.2%) and in the controls (86.5%). In one SS patient who developed parotid lymphoma, the US examination showed a hypoechoic 'cobblestones'-like inhomogeneous internal pattern which was coupled with an almost homogeneous MRI pattern. CONCLUSIONS: MRI appears unnecessary as a routine method in the diagnosis of SS; US examination is suitable both for the diagnosis and follow-up of SS. The above combination of the seemingly contradictory US and MRI findings is highly characteristic of lymphoma which has developed in the course of the disease.

[Evaluation of the nature of brain tumors using methods of nuclear medicine]. / Agydaganatok természetének vizsgálata nukleáris medicinai módszerekkel.

FDG-PET studies permit an assessment of the degree of brain tumour malignancy and detection of tumour recurrence. MIBI-SPECT also affords promising results in this respect. In this work, the diagnostic value of MIBI-SPECT was compared with that of FDG-PET for the determination of primary brain tumours malignancy and the detection of recurrent brain tumours. SPECT and PET examination were carried out within a week in 14 patients (12 males, 2 females, mean age: 40 years, range 16-61 years) with brain tumours. Seven patients had a primary tumour, and in a further 7 MRI or the clinical signs and symptoms let to a suspicion of tumour recurrence. All tumours were verified histologically to be gliomas of grades I-IV. The SPECT and PET images were analysed visually and semiquantitatively. In 3 of the investigated 7 primary glioma patients, there was a visibly enhanced MIBI-positive cases, only one had an increased FDG uptake. In 4 of the 7 tumour recurrence cases, either the MIBI or the FDG uptake was visibly increased. All of these were histologically high-grade gliomas. In the remaining low grade tumours (primary of recurrent), neither MIBI nor FDG revealed a pathologically increased uptake. The intensity of radiopharmaceutical uptake at the site of the tumours was visually and semiquantitatively higher for MIBI that for FDG. It is concluded that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours, showing increased uptake of MIBI according to the malignancy and tumour recurrence of brain tumours.

Intraventricular hemorrhage as a false localizing sign of a thoracolumbar arteriovenous malformation: case report.

BACKGROUND: Spinal arteriovenous malformation (SAVM) is a relatively rare disease characterized by a high incidence of intramedullary and subarachnoid haemorrhage. When the hemorrhage is profuse and the SAVM is in the cervical region the symptoms (disturbance of consciousness, papilledema, cranial nerve palsies, and convulsions) may be so severe and rapid in their onset that they may be mistaken for intracranial hemorrhage. We report here on a patient with a SAVM at T10-12, which bled intracranially, mainly intraventricularly, and resulted first in respiratory arrest and unconsciousness. CASE DESCRIPTION: The patient had been well until he was 28 years old when, during intercourse, he suffered a terrible headache and suddenly lost consciousness, with a transient respiratory arrest. He was also noted to have right hemiparesis. A computed tomography scan demonstrated intraventricular hemorrhage. After a 24-hour period of artificial ventilation the patient regained consciousness and the right arm paresis completely recovered, but a gradual worsening of the motor function of the left leg developed. Digital subtraction angiography did not demonstrate any intracranial source of bleeding, whereas spinal angiography revealed a SAVM located at the medullary cone, which was totally removed by surgery. CONCLUSION: The case reported here raises several important issues. First, the advisability of spinal magnetic resonance imaging in the investigation of intraventricular (and subarachnoid) hemorrhage in patients with no demonstrable intracranial source. Secondly, the benefits of early diagnosis and reestablishment of the spinal cord circulation before the onset of thrombosis and the progressive phase of myelopathy. Finally, the necessity of complete obliteration and treatment of SAVMs even in patients with fixed neurologic deficits, because rebleeding of lower thoracic or lumbar SAVMs can lead to impairment at a higher level with severe or lethal consequences.

Wernicke's encephalopathy induced by hyperemesis gravidarum.

A report is presented on a patient with Wernicke's encephalopathy secondary to hyperemesis gravidarum. The 25-year-old female presented 11 weeks into pregnancy with prolonged vomiting. Neurological examination 8 weeks later demonstrated obtunded sensations, nystagmus and ataxia of gait. MR imaging revealed bilateral lesions in the mediodorsal nuclei of thalami, in the hypothalamus and in the periaqueductal gray matter (1). The neurological signs and the MRI findings pointed to a diagnosis of Wernicke's encephalopathy. The patient was treated with intramuscular vitamin B1 followed by oral thiamine until the end of pregnancy. The subsequent course of the pregnancy was uncomplicated, and resulted in the delivery of a healthy 2970 g male infant. A review of the literature published during the last 30 years revealed an additional 20 cases of Wernicke's encephalopathy induced by hyperemesis gravidarum. Only half of these pregnancies resulted in the birth of a normal infant.

[Management of trigeminal neuralgia by microvascular decompression]. / Trigeminus neuralgia kezelése microvascularis dekompresszióval.

The experience with a series of 28 posterior fossa exploration and microvascular decompression for trigeminal neuralgia is presented. All the patients were treated with carbamazepine previously and some of them were operated on by destructive methods. The diagnostic work-up consisted of an accurate history, CT or MRI in all cases, and recently (in 17 cases) the vascular compression of the trigeminal nerve was demonstrated directly by MR angiography in the plane of the trigeminal nerve. Microvascular decompression was performed through a suboccipital retromastoid craniotomy. At the operations 21 arterial, 4 venous, 2 combined (arterial + venous) and 1 arachnoid band compression were found. The mean follow up was 30 months. Immediate pain relief was achieved in all cases but one, and there were two recurrences 6 and 12 months later (both of them were venous compression), which have been controllable medically since then. There were 3 permanent hypaesthesia of the face (one of them loss of corneal reflex), 2 hypacusis, 1 cerebrospinal fluid leakage and 1 cerebellar edema as complications. Microvascular decompression is a safe and effective treatment for trigeminal neuralgia and advised if the medical treatment is failed, the patient suitable for general anaesthesia, and there is the evidence of vascular compression of trigeminal nerve on MR angiography.

Moyamoya with arterial anomalies: relevance to pathogenesis.

We report five patients with moyamoya associated with arterial anomalies, including five aneurysms, one with ectasia of the parent artery, a basilar artery fenestration and an arteriovenous malformation. Possible pathogenetic factors for moyamoya are discussed, and a prenatal origin is suggested.