Dipole Localization and Test-Retest Reliability of Frequency and Duration Mismatch Negativity Generator Processes

The mismatch negativity (MMN) is an event related potential component elicited by changes in duration, frequency or intensity of the stimuli during repetitive series of equal standard stimuli. In the present study we compared duration and frequency MMN using dipole source analysis concerning both the test-retest reliability of MMN-amplitudes and the locations of the potential sources. Furthermore, the influence of attention for test-retest-reliability was studied. Therefore, two groups of healthy subjects were investigated with different attentional manipulations. Twenty-one healthy subjects had to perform a visual attention task during the recording and 21 healthy subjects had no additional task to perform. All subjects were studied twice with a time interval of 3 weeks. Test-retest reliability was sufficiently high for the frequency but slightly lower for the duration MMN. The locations of the frequency and duration MMN-dipoles were in the auditory cortex with a more anterior and caudal location for the frequency MMN-dipoles. The latter finding supports the hypothesis that the frequency and duration MMNs have separate neuronal generators.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Effects of 15-hydroperoxyeicosatetraenoic acid on human lymphocyte sheep erythrocyte rosette formation and response to concanavalin A associated with HLA system

The lipoxygenase product hydroperoxyeicosatetraenoic acid (HPETE) has immunosuppressive properties in vitro and in vivo. It was observed that 15-HPETE inhibit the sheep red blood cell rosette formation and the concanavalin A-induced blast transformation of human lymphocytes. This inhibition was HLA-linked. HLA-B12 subjects were less sensitive than non-B12 subjects. It is likely that HPETE acids are macrophage mediators which inhibit some lymphocyte functions.     

Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma

Summary Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and ₂-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor- in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.     

Diagnosis and treatment of risk factors in Germany and the UK

Objective

To estimate the impact of different systems of family practitioners’ payment on process of care: fee-for-service vs. capitation.

Design

Cross sectional international survey using cardiovascular prevention as an indicator of the quality of care.

Setting

Family physicians’ practices in Germany (fee-for-service) and the UK (capitation).

Subjects

778 patients attending for consultation regardless of morbidity or risk factor status.

Main outcome measures

Intervals since last consultation, since last BP-measurement, prevalence of known hypertension.

Results

There is a higher overall level of activity under FFS, but under capitation FPs seem to concentrate their efforts on the more severely ill or at risk. This would explain that under different systems of remuneraton the quality of care (outcome) is usually similar.

Conclusions

In areas of uncertainty FFS seems to stimulate activity or intervention, whereas under capitation FPs are rather reluctant to engage in procedures or interventions that are not sufficiently evaluated. Under prepaid remuneration FPs adjust in a way that the quality of care does not suffer.     

Presynaptic α2A-adrenoceptors inhibit the release of endogenous dopamine in rabbit caudate nucleus slices

₂-Adrenoceptors modulating the release of dopamine were identified and characterized in slices of the head of the rabbit caudate nucleus. Release of endogenous dopamine was measured by fast cyclic voltammetry as the increase in the extracellular concentration of dopamine elicited by electrical stimulation. The electrochemical signal was identified as dopamine by means of the oxidation potential, the voltammogram and the fact that the signal was not changed by desipramine, which inhibits the high affinity uptake of noradrenaline, but was greatly increased by nomifensine, which in addition inhibits the high affinity uptake of dopamine.Stimulation by 6 pulses/100 Hz increased the extracellular concentration of dopamine by about 85 nM. The selective ₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced this release with an EC₅₀ of 173 nM and by maximally 75%. The ₂-adrenoceptor agonists clonidine and oxymetazoline only tended to cause a decrease. Six drugs, including oxymetazoline, were tested as antagonists against UK 14,304. Their order of antagonist potency (pK_D values in brackets) was rauwolscine (8.0) > oxymetazoline (7.5) > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; 7.3) > phentolamine (7.1) > corynanthine (5.1) prazosin (< 6). Given alone, the antagonists did not change the release of dopamine elicited by 6 pulses/100 Hz, and the same was true for the dopamine receptor antagonist sulpiride. When caudate slices were stimulated by 10 pulses/1 Hz, sulpiride increased the release of dopamine. Desipramine and rauwolscine, in contrast, again caused no change.It is concluded that dopaminergic axons in the rabbit caudate nucleus possess release-inhibiting ₂-adrenoceptors. The antagonist affinities indicate that they belong to the _2A subtype. In this, they agree with all presynaptic ₂-autoreceptors studied so far in rabbits as well as with the ₂-heteroreceptors modulating the release of serotonin in rabbit brain cortex, suggesting that at least the majority of presynaptic ₂-adrenoceptors in the rabbit are _2A. The agonist sensitivity of the caudate presynaptic ₂-adrenoceptors is low in comparison with cerebrocortical presynaptic ₂-autoreceptors, possibly due to absence of a receptor reserve. Correspondence to: N. Limberger at the above address     

Lead-induced blockade of kainate-sensitive receptor channels

The effects of bivalent lead on ion channels activated by kainate and -amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) were studied using Xenopus oocytes microinjected with mRNA from rat brain. Lead reduced kainate-induced membrane currents in a reversible and dose-dependent manner, without affecting membrane currents induced by AMPA. Lead decreased the kainate currents with a concentration of 0.1 mol/l to 0.93 ± 0.01 and with a concentration of 100 mol/l to 0.41 ± 0.04 of the control values. The blocking effect of lead on kainate responses was voltage dependent. The inhibition was strongest at - 90 mV to - 70 mV and became weaker at more positive membrane potentials. The effect of lead on the kainate-induced membrane currents remained unchanged when the concentration of kainate was increased. Hence lead probably represents a noncompetitive channel-blocking agent for non-N-methyl-d-aspartate (NMDA) receptor channels activated by kainate.     

Comparison of four magnetic resonance methods for mapping small temperature changes

Non-invasive detection of small temperature changes (< 1 degree C) is pivotal to the further advance of regional hyperthermia as a treatment modality for deep-seated tumours. Magnetic resonance (MR) thermography methods are considered to be a promising approach. Four methods exploiting temperature-dependent parameters were evaluated in phantom experiments. The investigated temperature indicators were spin-lattice relaxation time T1, diffusion coefficient D, shift of water proton resonance frequency (water PRF) and resonance frequency shift of the methoxy group of the praseodymium complex (Pr probe). The respective pulse sequences employed to detect temperature-dependent signal changes were the multiple readout single inversion recovery (T One by Multiple Read Out Pulses; TOMROP), the pulsed gradient spin echo (PGSE), the fast low-angle shot (FLASH) with phase difference reconstruction, and the classical chemical shift imaging (CSI). Applying these sequences, experiments were performed in two separate and consecutive steps. In the first step, calibration curves were recorded for all four methods. In the second step, applying these calibration data, maps of temperature changes were generated and verified. With the equal total acquisition time of approximately 4 min for all four methods, the uncertainties of temperature changes derived from the calibration curves were less than 1 degree C (Pr probe 0.11 degrees C, water PRF 0.22 degrees C, D 0.48 degrees C and T1 0.93 degrees C). The corresponding maps of temperature changes exhibited slightly higher errors but still in the range or less than 1 degree C (0.97 degrees C, 0.41 degrees C, 0.70 degrees C, 1.06 degrees C respectively). The calibration results indicate the Pr probe method to be most sensitive and accurate. However, this advantage could only be partially transferred to the thermographic maps because of the coarse 16 x 16 matrix of the classical CSI sequence. Therefore, at present the water PRF method appears to be most suitable for MR monitoring of small temperature changes during hyperthermia treatment.     

Uveal melanoma: correlation of histopathologic and radiologic findings by using thin-section MR imaging with a surface coil

PURPOSE: To evaluate whether the different signal intensities at magnetic resonance (MR) imaging of melanoma are associated with a higher content of melanin. MATERIALS AND METHODS: In a prospective study, MR imaging and ophthalmoscopic examination findings in 42 patients (19 women, 23 men; age range, 30-87 years) with uveal melanoma were compared with histopathologic examination findings obtained after enucleation. MR imaging was performed with 2-mm sections by using a 5-cm surface coil. T1- and T2-weighted images were obtained before and after contrast material administration. RESULTS: In 33 (79%) of the patients, there was homogeneous tumor pigmentation, whereas in nine (21%) patients, there was inhomogeneous bipartite tumor pigmentation. Compared with the histopathologic data, the results of qualitative evaluation were accurate in 29 (58%) of 50 and in 26 (53%) of 49 tumorous areas on T1- and T2-weighted images, respectively. Quantitative evaluation yielded better results, especially at T1-weighted imaging; an 86% correlation was found. Because of methodological reasons, only the superficial pigmentation of inhomogeneous tumors could be evaluated with ophthalmoscopy. CONCLUSION: Thin-section MR imaging of the eye enables an accurate prediction of melanomatous pigmentation with quantitative evaluation of plain T1-weighted images and is superior to ophthalmoscopy in cases of inhomogeneous pigmentation.