Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

Identification of endothelial and mesothelial cells in human omental tissue and in omentum-derived cultured cells by specific cell markers.

Human omental tissue has been used as a source for the isolation and cultivation of microvascular endothelial cells, but also for mesothelial cells. Since both cell types have several morphologic and functional features in common, concerns were raised whether endothelial cells can be separated from mesothelial cells by the methods described for the isolation of microvascular endothelial cells. In the present study, endothelial cells were identified in the capillaries of native human omentum by several endothelial-cell specific markers. von Willebrand factor was demonstrated by polyclonal and monoclonal antibodies, a lectin-specific ligand by Ulex europaeus I, and an endothelial-cell specific surface epitope by the monoclonal antibody, PAL-E. These markers were not found positive with mesothelial cells of native omentum. Mesothelial cells were identified by monoclonal antibodies against the intermediate filaments, cytokeratin and vimentin. After having demonstrated the specificity of the methods for the distinction between endothelial and mesothelial cells within native omentum, these methods were applied to omentum-derived cells previously claimed to be microvascular endothelial cells. These cultured cells proved to be negative for von Willebrand factor, Ulex europaeus I ligand and PAL-E epitope. In contrast to this, the cultivated cells stained positive to cytokeratin and vimentin. Furthermore, it was shown by immunoprecipitation studies that omentum-derived cells did not synthesize and secrete vWF, indicating the nonendothelial nature of these cells. Finally, electron microscopy demonstrated microvilli on the surface of cultivated omentum-derived cells indicative for the mesothelial origin of these cells. The data presented demonstrate that the cells obtained using the previously published methods for the isolation and cultivation of "microvascular endothelial cells" from omental tissue are of mesothelial and not of endothelial origin. Thus, a great number of data obtained with this type of omentum-derived cells thought to be microvascular endothelial cells need re-evaluation.     

Interpretation of antitoxoplasma antibody findings

Between reactions assessing one class of immunoglobulins and reactions detecting all serum immunoglobulins comprehensively such as CFT, there is, as might be expected, a very poor quantitative correlation and thus in individual sera the result of one reaction cannot be reliably added to the result of another (CFT:ELISA/IgG). Even the correlation between reactions focused on the same Ig class (ELISA/IgG: IFT/IgG) is no better. Among reactions assessing specific IgM we consider ELISA/IgM better than IFT/IgM because there is not the risk of false negativity caused by concurrence of IgG. A combination of ELISA/IgG and ELISA/IgM gives good results as a statistical group: the distribution of results revealed agglomerations of sera corresponding to the assumed age of the infection derived from the generally accepted pattern of antibody formation. The applicability of the combination of these two reactions alone for evaluation of individual sera is a promising procedure but awaits further confirmation. Long-term investigations revealed within two years after infection a marked decline of CFT antibodies in the majority of cases but it was not sufficiently clear in ELISA/IgG. Despite the technical advantages of ELISA reactions, elimination af the CFT reaction is not foreseen in the near future. As the minimal combination of methods which provides adequate information we may consider at the present time CFT for assessment of total antibodies and ELISA/IgM for more marked differentiation of the acute stage. Evaluation of the lowest CFR titres considered hitherto as "practically negative" must be obviously revised in subjects with immunosuppression and organ donors for transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Side effects of laxatives]

The side effects of anthraquinones, diphenylmethane derivatives (e.g. bisacodyl, sodium picosulphate), saline laxatives, lactulose, and cisapride are discussed. When taken in recommended doses, no relevant side effects have been observed, except for hypermagnesemia following magnesium containing cathartics in renal insufficiency. This holds also true for the time of pregnancy and lactation. (Pseudo-)melanosis coli is characterized by pigment loaded macrophages without apparent functional consequences. It occurs mainly after anthraquinones, but to a lesser degree also after diphenylmethane derivatives. Clinically relevant side effects of the above laxatives have been published exclusively after excessive dosing. They consist in electrolyte disturbances (mainly hypokalemia), metabolic alkalosis, renal tubular dysfunction, and other less frequent side effects. Cases of "cathartic colon" have not been published during the last decades. It was probably due to laxatives which are no longer used.     

Impaired tactile pattern recognition in the early stage of primary degenerative dementia compared with normal aging

Tactile pattern recognition of ten different patterns which were engraved upon 4 x 4 cm plastic plaquettes with one hand and thereafter drawing with the other or the same hand was tested in 21 patients with a mild stage primary degenerative presenile onset dementia of Alzheimer type (DAT) and in 14 patients with a questionable dementia on the background of a chronic cardiovascular disease (CVD) in comparison to 15 healthy subjects of the same age (51 years old, elder controls, (EC)) and 16 younger subjects (22 years old, younger controls, (YC)). Patients made about four times more errors than the EC group. Duration from the begin of touching to the end of drawing was significantly longer in patients than in controls. In a second task the subjects had to recognize four subsequent patterns, then to perform a standard multiplication task and afterwards to draw all four patterns in their correct sequence. Patients made about ten times more errors in pattern recognition and series reproduction than age-matched controls.     

Critical checking of the radiological diagnosis of "complete remission" and "partial remission" following induction chemotherapy of small-cell lung cancer in the light of postoperative histological examination.

A multimodal therapy concept for small-cell lung cancer, which for patients with established pretherapeutic homolateral lymph-node metastases (N2) prescribes induction chemotherapy with subsequent resection as well as supplemental chemo- and radiotherapy, provided the opportunity to evaluate histologically the radiological diagnoses "complete remission" and "partial remission" using resection specimens. In 17 patients a 75% to 100% reduction in tumor size was achieved according to radiological diagnosis. Predictions of "no evidence of disease" or "evidence of disease" were only correct in ten cases. In the remaining seven cases, histology showed the radiological findings to be incorrect. This gives a 77% sensitivity for radiological diagnosis with no specificity. Moreover, differentiation between therapy effect on the primary tumor and on the N2 metastases gives similar results: sensitivity 64% and 67% respectively, specificity 33% and 25% respectively. It is concluded that, particularly after the tumor responds well to therapy, radiological techniques are unsuitable for establishing a diagnosis of "no evidence of disease" or "evidence of disease" in small-cell lung cancer. This is because on the one hand the radiological methods available do not permit clear differentiation between vital tumor tissue and necrosis or fibrosis, while on the other hand groups of vital tumor cells beyond the resolution power of X-ray technology will escape detection.     

Mescaline-induced psychopathological, neuropsychological, and neurometabolic effects in normal subjects: experimental psychosis as a tool for psychiatric research.

The psychological, neuropsychological, and neurometabolic effects of the hallucinogenic agent mescaline were investigated in 12 normal men who were volunteers. Mescaline produced an acute psychotic state 3 1/2-4 hr after drug intake, as measured by the Brief Psychiatric Rating Scale (BPRS) and Paranoid Depression Scale (PDS). The Assessment of Altered States of Consciousness (APZ) questionnaire revealed specific effects of mescaline in the visual system. Neuropsychological effects were studied with a face/nonface decision task with known right-hemisphere advantage, in which mescaline induced a decrease of functioning of the right hemisphere. In functional brain imaging using single photon emission computed tomography (SPECT), mescaline produced a "hyperfrontal" pattern with an emphasis on the right hemisphere, which was correlated with mescaline-induced psychotic psychopathology. Our findings question the validity of the concept of hypofrontality as an explanation for schizophrenic symptomatology. The study of psychoactive substances under controlled laboratory conditions has the methodological advantage of intraindividual control, and hence, minimal variability of data.     

Dependence of presaccadic cortical potentials on the type of saccadic eye movement.

Premovement cortical potentials were studied with 4 types of saccadic eye movement: (a) visually triggered saccades of normal reaction time (RT; regular saccades); (b) visually triggered saccades of extremely short RT (express saccades); (c) saccades towards predicted target locations (anticipatory saccades); (d) saccades back towards predicted location of fixation point (refixation saccades). With all 4 saccade types a "presaccadic negativity" with the maximum at the vertex (Cz) was observed. A bilaterally symmetrical component contained in this potential (being smallest with almost unconsciously performed refixation saccades and smaller in trained than in naive subjects) appeared to be related mainly to the subjects' volitional effort. In addition, anticipatory and refixation saccades were preceded by an early, widespread contralateral negativity, which we relate to cortical activities that prepare, in general terms, action within or towards the hemifield containing the saccade goal. During the 60 msec before anticipatory saccades, a negativity occurred over the contralateral central lead, which may reflect neural activation in the frontal eye field (FEF) and premotor cortex. In contrast, regular saccades were preceded 30 msec before onset by a negativity over the contralateral parietal cortex, which probably reflects an activation of parietal visuo-motor neurons. No lateralization of the cortical potentials was observed before express saccades, which suggests that these saccades are generated in a reflex-like way mainly by subcortical mechanisms.     

Thalamic connections of the vestibular cortical fields in the squirrel monkey (Saimiri sciureus).

The afferent thalamic connections to cortical fields important for control of head movement in space were analysed by intracortical retrograde tracer injections. The proprioceptive/vestibular area 3aV, the neck-trunk region of area 3a, receives two thirds of its thalamic projections from the oral and superior ventroposterior nucleus (VPO/VPS), which is considered as the proprioceptive relay of the ventroposterior complex (Kaas et al., J. Comp. Neurol. 226:211-240, 1984). The parieto-insular vestibular cortex (PIVC, area retroinsularis, Ri) receives its main thalamic input from posterior parts of the ventroposterior complex and from the medial pulvinar. Anatomical evidence is presented that the posterior region of the ventroposterior complex is a special compartment within this principal somatosensory relay complex. The parietotemporal association area T3, mainly involved in visual-optokinetic signal processing, receives a substantial input from the medial, the lateral, and the inferior pulvinar. Dual tracer experiments revealed that about 5% of the thalamic neurons projecting to 3aV were spatially intermingled with neurons projecting to areas PIVC or T3. This spatial intermingling was distributed over small but numerous, circumscribed thalamic regions, called "common patches," which were found mainly in the intralaminar nuclei, the posterior group of thalamic nuclei, and the caudal parts of the ventroposterior complex. The "common patches" may indicate a functional coupling of area 3aV with the PIVC or area T3 on the thalamic level. In control experiments thalamic projections to the granular insula Ig and the anterior part of area 7, two cerebral structures connected with the vestibular cortical areas, were studied. Some overlap in the thalamic relay structures projecting to these areas with those projecting to the vestibular cortices was found. A quantitative evaluation of thalamic regions projecting to different cortical structures was performed by constructing so-called "thalamograms." A scheme was developed that describes the afferent thalamic connections by which vestibular, visual-optokinetic, and proprioceptive signals reach the vestibular cortical areas PIVC and 3aV.     

Assessment of intracranial hemodynamics in sleep apnea syndrome.

BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5-83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels.