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Biomedical subjects

S Vanhatalo

Publications and source records attributed to S Vanhatalo.

At least 19 recordsLinked to original sources

Evaluation of commercially available electrodes and gels for recording of slow EEG potentials.

OBJECTIVE: To test the applicability of different types of commercially available electrodes and electrode gels or pastes for recording of slow EEG potentials. METHODS: Experiments were carried out on six types of reusable electrodes (silver, tin and gold cup electrodes, sintered silver-silver chloride (Ag|AgCl), platinum, stainless steel), six disposable Ag|AgCl electrode models, and nine gels or pastes. We studied the parameters, which are critical in slow-potential recording, such as polarization, initial and long-term stability and low-frequency noise. RESULTS: The best results were obtained with the reusable sintered Ag|AgCl electrodes. The six disposable Ag|AgCl electrode models also proved to have appropriate electrical properties. Other types of reusable electrodes suffered from diverse degrees of polarization, baseline drift, low-frequency noise, high resistance, and changes in properties due to wear and tear. Seven out of nine gels or pastes contained a significant amount of chloride, which is a prerequisite for DC stability of Ag|AgCl electrodes, whereas the absolute concentration of chloride had little effect. CONCLUSIONS: Direct current (DC) coupled recording of EEG is critically dependent on the choice of electrode and gel. SIGNIFICANCE: Our results provide rigorous criteria for choosing DC-stable electrodes and gels for DC-coupled or long time-constant AC-coupled recordings of slow EEG potentials.

Electrodes↗

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep.

Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of interictal events. Here we use direct current electroencephalography to demonstrate large-scale infraslow oscillations in the human cortex at frequencies ranging from 0.02 to 0.2 Hz. These oscillations, which are not detectable in conventional electroencephalography because of its limited recording bandwidth (typical lower limit 0.5 Hz), were observed in widespread cortical regions. Notably, the infraslow oscillations were strongly synchronized with faster activities, as well as with the interictal epileptic events and K complexes. Our findings suggest that the infraslow oscillations represent a slow, cyclic modulation of cortical gross excitability, providing also a putative mechanism for the as yet enigmatic aggravation of epileptic activity during sleep.

Adolescent↗

Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle.

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

Administration, Oral↗

Cerebrospinal fluid insulin-like growth factor-1, insulin growth factor binding protein-2 or nitric oxide are not increased in MS or ALS.

OBJECTIVES: Many studies have shown that nitric oxide (NO) and growth factors including insulin growth factors (IGFs) may be involved in the pathogenesis of multiple sclerosis (MS) and neurodegenerative diseases. Our previous studies suggested a relationship between cerebrospinal fluid (CSF) NO metabolites (nitrates and nitrites, NN(x)) and IGF-1 in patients with progressive encephalopathy, hypsarrhythmia and optic atrophy syndrome. MATERIAL AND METHODS: We examined CSF concentrations of NN(x), IGF-1 and IGF binding protein-2 (IGFBP-2) in 25 controls, 14 patients with MS and 14 patients with amyotrophic lateralis sclerosis (ALS). RESULTS: There were no significant differences in CSF levels of NN(x), IGF-1 or IGFBP-2 between the groups. CSF IGFBP-2 concentrations correlated significantly with age in controls, which may reflect age-related changes in the blood-brain barrier function. CONCLUSION: Upregulation of the production of NO and IGF-1 in the brain or spinal cord does not influence CSF levels of these molecules in MS or ALS.

Adolescent↗

Very slow EEG responses lateralize temporal lobe seizures: an evaluation of non-invasive DC-EEG.

BACKGROUND: This study tested the idea that very slow EEG responses (direct current [DC] potential shifts) could be detected noninvasively during temporal lobe (TL) seizures, and that these shifts give lateralizing information consistent with that obtained by other methods. METHODS: Seven patients with TL epilepsy (TLE) were recorded with scalp DC-EEG technique at bedside. All recordings were performed simultaneously with conventional EEG (scalp in five, and intracranially in two; two patients with scalp recordings were recorded intracranially later). Seizures in five patients originated in the mesial TL. Ictal DC shifts were evaluated by comparing them to the temporal evolution of ictal discharges, and by comparing the laterality of these shifts to the side of seizure onset defined by routine EEG and other presurgical diagnostic tests. RESULTS: All seizures (35/35) were associated with negative DC shifts at temporal derivations (30 to 150 micro V relative to vertex), beginning at the electrical seizure onset, and lasting for the whole seizure. In eight seizures (five patients) with documented mesial TL onset, the polarity of the DC shift was initially positive followed by a negative one after lateral spread of seizure activity. In all cases, the side of the EEG shift agreed with other diagnostic tests, and, at times, was more clearly lateralized than the conventional scalp EEG. CONCLUSIONS: DC-EEG recordings are practical and achievable at the bedside. Ictal DC shifts are consistently observed in scalp recordings in TL seizures, and reliably lateralize them. This method may hold promise in reducing the need for invasive monitoring in patients with TLE where other noninvasive tests are equivocal.

Adult↗

Topography and elimination of slow EEG responses related to tongue movements.

This study aimed to characterize the topography and mechanism of slow EEG potentials related to tongue movement (TMP), and to devise a method for their elimination. Eight adult subjects were recorded with 8-channel direct current (DC) EEG (n = 5) or with a 256-channel, dense array EEG (n = 4). Subjects were requested to push their tongue toward the incisors in a closed mouth. We examined the time course and topography of the ensuing TMP. The underlying mechanism and elimination of TMP were studied by electrical isolation of the tongue with a latex sheet, and by short-circuiting of tongue to gingival pouch. Forward movement of the tongue caused global changes in scalp potentials, with frontal areas more positive, and the strongest gradients between the mastoid region and other scalp areas. Scalp current source density was highest near ear canals and orbital fossae. Electrical isolation of the tongue tip with a latex sheet resulted in a near-complete elimination of TMPs, while short-circuiting resulted in high amplitude responses, suggesting that TMPs are caused by a change in the geometry of conductive pathways. Our results indicate that significant scalp potentials are caused by even modest tongue movements, which may occur subconsciously during various cognitive tasks. The topography and small amplitude of TMPs make their off-line rejection difficult, while an isolation method of the kind used here may substantially diminish TMP artifacts in studies on slow cognitive potentials.

Adult↗

Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain.

OBJECTIVE: To study whether hemodynamic changes in human brain generate scalp-EEG responses. METHODS: Direct current EEG (DC-EEG) was recorded from 12 subjects during 5 non-invasive manipulations that affect intracranial hemodynamics by different mechanisms: bilateral jugular vein compression (JVC), head-up tilt (HUT), head-down tilt (HDT), Valsalva maneuver (VM), and Mueller maneuver (MM). DC shifts were compared to changes in cerebral blood volume (CBV) measured by near-infrared spectroscopy (NIRS). RESULTS: DC shifts were observed during all manipulations with highest amplitudes (up to 250 microV) at the midline electrodes, and the most pronounced changes (up to 15 microV/cm) in the DC voltage gradient around vertex. In spite of inter-individual variation in both amplitude and polarity, the DC shifts were consistent and reproducible for each subject and they showed a clear temporal correlation with changes in CBV. CONCLUSIONS: Our results indicate that hemodynamic changes in human brain are associated with marked DC shifts that cannot be accounted for by intracortical neuronal or glial currents. Instead, the data are consistent with a non-neuronal generator mechanism that is associated with the blood-brain barrier. SIGNIFICANCE: These findings have direct implications for mechanistic interpretation of slow EEG responses in various experimental paradigms.

Adult↗

Dutch patients with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome.

PEHO syndrome (progressive encephalopathy, peripheral edema, hypsarrhythmia, and optic atrophy) is a neurodegenerative disorder first characterized in Finnish patients. Subsequent reports have occasionally identified cases of PEHO occurring in some other countries. We describe two Dutch children who represent the first reported cases with PEHO syndrome from western Europe. Both of these children showed typical characteristics of the syndrome, including generalized hypotonia and edema of their faces and extremities, profound psychomotor retardation, progressive cerebellar atrophy, and severe epilepsy which initially started as infantile spasms. Our experience has shown that distinguishing cases with true PEHO from those with other, clinically similar disorders requires a firm demonstration of both the presence and the progress of typical neuroradiological findings. Our present cases suggest that 1) PEHO syndrome is not limited to Finnish heritage, and that 2) many more patients with PEHO could be identified with increased knowledge of the syndrome.

Brain Damage, Chronic↗

Evidence for nodose ganglion as the source of innervation to the anterior lobe of the pituitary gland.

Recent studies have provided convincing evidence for the presence of peptidergic nerve fibers in the pituitary anterior lobe in several animal species. This study was aimed at elucidating the origin of this innervation by neuroanatomical tracing, denervation experiments, and immunohistochemistry. Immunohistochemistry against substance P and growth-associated protein 43 revealed a dense fiber plexus within the anterior lobe, and these markers were mostly colocalized. Retrograde tracing with Fluorogold from the pituitary gland stained neurons in the hypothalamus, superior cervical ganglia and the nodose ganglia. None of the Fluorogold-labelled neurons in the hypothalamus or superior cervical ganglion were substance P-immunoreactive, while many of the neuronal cell bodies in the nodose ganglion exhibited substance P immunoreactivity. There were no Fluorogold-labelled neurons in the trigeminal, otic or cervical dorsal root ganglia. Surgical transection of the pituitary stalk or bilateral removal of the superior cervical ganglion did not abolish the anterior lobe nerve fibers, and anterograde tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine perchlorate from the pituitary stalk failed to stain any nerve fibers within the anterior lobe. Our findings suggest that the nodose ganglion neurons likely innervate the pituitary anterior lobe, while neither hypothalamus nor sympathetic superior cervical ganglion may be a source of this innervation. By showing a distinct neuronal system in the pituitary anterior lobe our findings (i) support the previous functional studies demonstrating a distinct regulation of the morphology of the anterior lobe innervation by hormonal changes, and (ii) suggest that the innervation of the pituitary anterior lobe is a part of the visceral innervation by the vagus nerve rather than a part of the other intracranial innervation. These findings provide a neuroanatomic basis for the reported observations about the neural regulation of the pituitary anterior lobe.

Animals↗

Nitric oxide metabolites, nitrates and nitrites in the cerebrospinal fluid in children with west syndrome.

Nitric oxide (NO) has been implicated in the mediation of the neuronal excitotoxic cascade. In order to estimate brain NO production, cerebrospinal fluid (CSF) levels of NO metabolites, nitrates and nitrites (NN(x)) were measured in 31 children with west syndrome (WS) and in 12 controls. There was no age-related change in the NN(x) levels during the first year of life. The mean of the NN(x) levels was significantly higher in patients with WS than in controls (8.43 vs. 5.27 microM; P=0.01). Analysis of the etiological subgroups showed that the patients with a symptomatic etiology of WS had significantly higher NN(x) levels than controls (P<0.005) or than the patients with a cryptogenic etiology. The cryptogenic cases, in turn, did not differ from the controls (P=0.48). Levels of NN(x) were also significantly higher in children with focal brain abnormalities (infarction, atrophy or previous infection) than in those with other abnormalities or with normal neuroradiological findings (P<0.005). No correlation was found between the NN(x) levels and the duration of the symptoms, while paired samples obtained from eight children with WS showed that the NN(x) levels rose significantly (P=0.02) within the first 40 days of symptoms. The levels of NN(x) did not correlate with the CSF levels of neuronal growth factor or with the later decline in mental performance. This study demonstrates that the production of NO can be measured in human epileptic conditions and supports the idea gained from experimental studies that NO is involved in the pathophysiology of epilepsy. However, normal levels of NN(x) in patients with cryptogenic infantile spasms suggest that an increase in NO production be due to the concomitant neuronal damage rather than seizure activity per se. The findings suggest that there are no age-related changes in the NN(x) levels during the first year of life, and that children with symptomatic WS have elevated levels of NN(x), which rise during the first 40 days of symptoms. Although the NN(x) levels cannot be used to estimate the duration of symptoms or to predict the prognosis of mental development, they may support the differentiation of symptomatic from cryptogenic etiologies of WS.

Analysis of Variance↗

Reversed visual field constrictions in children after vigabatrin withdrawal--true retinal recovery or improved test performance only?

While vigabatrin-associated visual field constrictions have been generally considered irreversible, some case reports have raised the hope of partial improvement after drug withdrawal in occasional patients. Here we describe seven children with epilepsy, whose visual field constrictions, as demonstrated by the kinetic perimetry (Goldmann), attenuated or recovered after discontinuation of vigabatrin therapy. While this improvement may be largely due to better performance in later test sessions, we want to raise the possibility that some visual field recovery may be possible at least in young patients.

Adolescent↗

Nitric oxide synthase immunoreactivity in the rat hippocampus after status epilepticus induced by perforant pathway stimulation.

Nitric oxide has recently been implicated in mediation of neuronal excitotoxicity and damage. This study aimed at elucidating the changes in the expression of neuronal isoform of nitric oxide synthase (nNOS) in the hippocampus after status epilepticus induced by perforant pathway stimulation. nNOS-immunoreactivity (nNOS-ir) and neuronal damage, assessed by silver staining, were evaluated separately in different hippocampal subfields 2 weeks after induction of status epilepticus. Perforant pathway stimulation resulted in an increase in the number of nNOS-immunoreactive neurons in the stratum radiatum of the CA1 and CA3 subfields of the hippocampus proper, and the hilus of the dentate gyrus. The morphology and distribution of the nNOS-ir neurons resembled that of interneurons. No correlation of the number of nNOS-ir neurons to the neuronal damage score was observed. Our results suggest that status epilepticus provokes a de novo expression of nNOS protein, and the nNOS expressing neurons may be selectively resistant to epileptic brain injury.

Animals↗

Neurturin is a neurotrophic factor for penile parasympathetic neurons in adult rat.

Neurturin (NRTN), a member of the GDNF family of neurotrophic factors, promotes the survival and function of several neuronal populations in the peripheral and central nervous system. Recent gene ablation studies have shown that NRTN is a neurotrophic factor for many cranial parasympathetic and enteric neurons, whereas its significance for the sacral parasympathetic neurons has not been studied. NRTN signals via a receptor complex composed of the high-affinity binding receptor component GFRalpha2 and the transmembrane tyrosine kinase Ret. The aim of this study was to determine whether NRTN could be an endogenous trophic factor for penis-projecting parasympathetic neurons. NRTN mRNA was expressed in smooth muscle of penile blood vessels and corpus cavernosum in adult rat as well as in several intrapelvic organs, whereas GFRalpha2 and Ret mRNAs were expressed in virtually all cell bodies of the penile neurons, originating in the major pelvic ganglia. (125)I-NRTN injected into the shaft of the penis was retrogradely transported into the major pelvic and dorsal root ganglia. Mice lacking the GFRalpha2 receptor component had significantly less nitric oxide synthase-containing nerve fibers in the dorsal penile and cavernous nerves. In conclusion, these data suggest that NRTN acts as a target-derived survival and/or neuritogenic factor for penile erection-inducing postganglionic neurons.

Animals↗

Glial cell line-derived neurotrophic factor is expressed in penis of adult rat and retrogradely transported in penile parasympathetic and sensory nerves.

Glial cell line-derived neurotrophic factor (GDNF), a member of the GDNF family of neurotrophic factors, promotes the survival and function of several neuronal populations in the peripheral and central nervous system. In the present study, expression of GDNF mRNA in the shaft of adult rat penis is demonstrated. In situ hybridization revealed GDNF mRNA expression in cells lying in the narrow zone between the tunica albuginea and the cavernous tissue. Most subtunical cells exhibited immunoreactivity for vimentin and S100 beta, but they did not stain for smooth muscle alpha actin or PGP9.5. This suggests that the GDNF mRNA-expressing cells may have a mesenchymal origin. Also retrograde axonal transport of intracavernously injected 125I-labeled GDNF in penile parasympathetic and sensory neurons is shown. The transport was inhibited by excess unlabeled GDNF, whereas excess cytochrome c had no effect. This is in agreement with the view that the transport was mediated by binding to specific receptors located on axon terminals. In addition, this study demonstrates expression of GDNF family receptor-alpha 3 (GFR alpha 3) mRNA in most adrenergic, but only in a minor part (5.3%) of the penis-projecting adult rat major pelvic ganglion neurons, as well as in almost half (45.6%) of the penile S1 dorsal root ganglion neurons. In conclusion, the present data suggest that GDNF may act as a neurotrophic factor for subpopulations of adult rat penile parasympathetic and sensory neurons.

Animals↗

Fetal pain?

During the last few years a vivid debate, both scientifically and emotionally, has risen in the medical literature as to whether a fetus is able to feel pain during abortion or intrauterine surgery. This debate has mainly been inspired by the demonstration of various hormonal or motor reactions to noxious stimuli at very early stages of fetal development. The aims of this paper are to review the literature on development of the pain system in the fetus, and to speculate about the relationship between "sensing" as opposed to "feeling" pain and the number of reactions associated with painful stimuli. While a cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions much earlier. However, more important than possible painfulness is the fact that the noxious stimuli, by triggering stress responses, most likely affect the development of an individual at very early stages. Hence, it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies. A clinically relevant aim is rather to avoid and/or treat any possibly noxious stimuli, and thereby prevent their potential adverse effects on the subsequent development.

Brain↗

No colocalization of immunoreactivities for VIP and neuronal NOS, and a differential relation to cGMP-immunoreactivity in bovine penile smooth muscle.

The distribution of immunoreactivity (IR) for the neuropeptide vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the bovine retractor penis muscle (RP) and penile artery (PA) was studied by using two different methods. The distribution of these immunoreactivities was also compared with that of the immunoreactivity for cyclic guanosine monophosphate (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had a distribution that was completely different from that of the nerve fibers and terminals immunoreactive for nNOS. This contrasts with the previous observations in penile smooth muscle of other species. In the RP, as well as in the PA, many of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR in the nerve fibers and terminals innervating penile smooth muscle show wide species differences. They also suggest that the mechanisms by which VIP could be involved in neurogenic penile erection may vary between species.

Animals↗