Objective: To explore the stability of diverse manic presentations across manic recurrences.
Method: A total of 253 bipolar patients who experienced two or more hospitalizations, because of ...consecutive manic (or mixed) episodes, during a 20‐year period were included. All patients had second hospitalizations with an mean interval of 773 days, while 126 and 91 patients had third and fourth hospitalizations with mean intervals of 1559 and 2237 days from the index hospitalization, respectively. Seven symptom scores, previously factor‐validated, were calculated.
Results: Depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis were moderately correlated across the index and subsequent hospitalizations.
Conclusion: A majority of diverse manic presentations were stable across manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long‐term course of bipolar disorder. The finding may serve for the development of more effective long‐term treatment strategies and a clinically more reasonable subtyping of mania.
Many studies have shown a high prevalence of discrete neuromotor disturbances in schizophrenic patients. It was hypothesized that these disturbances are lateralized and reflect a neurodevelopmental ...disorder underlying schizophrenia. A new method for assessing subtle motor dysfunction and hemispheric asymmetries is the registration of hand movements with a digitizing tablet. Using this method, we studied hand–motor dysfunction and its lateralization in schizophrenics, as compared with healthy controls.
All subjects (27 schizophrenic patients, 13 of them without neuroleptic medication, the others under neuroleptics; 31 healthy controls) drew super-imposed concentric circles. We computed kinematic parameters reflecting velocity and automatization to quantify neurological soft signs (NSS).
The patients had significant impairments of regularity of repetitive hand movements, as compared with the healthy controls (F≥5.35;
p≤0.024
∗). Comparing differences of left- and right-hand performance between patients and controls, we found longer stroke duration (
F=(15,98);
p=0.000***) and decreased automatization (
F=18,14;
p=0.000***), especially on the left side in schizophrenic patients.
Measuring hand movements with a digitizing tablet is a sensitive method for assessing subtle motor dysfunction in schizophrenic patients, not reflected in the scores of clinical scales. Our findings show NSS in schizophrenic patients, independently of neuroleptics. Further, the hypothesis of lateralization of cerebral structures generating NSS towards the right hemisphere in schizophrenia is supported.
In 12 patients with affective disorders (ICD-10: F31, F32, F33), EEGs were recorded before and after 4.4 months of lithium treatment. Effects of lithium on the EEG were analyzed by power spectral ...analysis controlled for vigilance. We found (1) an increase in relative power in both delta and theta band which was related to the lithium plasma level, (2) a decrease in relative alpha power especially at occipital leads and (3) a reduction of the dominant alpha frequency. The changes in relative power were more pronounced in the right hemisphere, which is in contrast to the hypothesis of a site-specific localization of lithium effects only in left anterior regions.
Muscarinic M2 acetylcholine receptors contain an allosteric site that is probably located at the entrance of the ligand binding pocket above the orthosteric binding site. With the orthosteric area ...not occupied, allosteric agents might gain access to this site. The interaction of allosteric agents with orthoster-occupied receptors is known to depend on the buffer conditions in an alloster-specific fashion. Utilizing the buffer-dependent potency shift as an indicator, we aimed to find out for two rod-like shaped and flexible allosteric agents whether or not there is evidence for a switch in the site of attachment in free compared with 3HN-methylscopolamine (3HNMS)-occupied porcine heart M2 receptors. These agents are the bispyridinium compounds WDuo3 (1,3-bis4-(phthalimidomethoxyimino-methyl)-pyridinium-1-yl propane dibromide) and Duo3 (4,4'-bis-(2,6-dichloro-benzyloxy-imino)-methyl-1,1'-propane-1,3-diyl-bis-pyridinium dibromide). The prototype allosteric agents gallamine and alcuronium were included. Inhibition of 3HNMS association was taken to reflect alloster interaction with free receptors, inhibition of 3HNMS dissociation indicated binding to 3HNMS-occupied receptors. In Na,K,Pi buffer (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4 at 23 degrees C) compared with Mg,Tris,Cl,Pi buffer (45 mM Tris-HCl, 2.6 mM MgHPO4, pH 7.3 at 37 degrees C) WDuo3 underwent the same loss of potency for the interaction with either free or 3HNMS-liganded receptors. The loss of potency was quantified by a potency ratio (PR), i.e. the ratio between the concentrations of the modulator leading to a half-maximal delay of 3HNMS association or dissociation, respectively, in Mg,Tris,Cl,Pi compared with Na,K,Pi. For WDuo3 the ratios were PRass=27 and PRdiss=22, respectively. For Duo3, the interaction with free and 3HNMS-occupied receptors only slightly depended on the composition of the incubation medium: PRass=1.3, PRdiss=2.8. In contrast to the other agents, the concentration-effect curves of which had slope factors nH not different from unity, the curves of Duo3 were steep (nH about -1.6). For alcuronium the shift factors amounted to PRass=29 and PRdiss=25, for gallamine to PRass=216 and PRdiss=159. In conclusion, there was a wide variation between the allosteric agents with regard to the respective buffer dependence of action. Yet, for a given allosteric agent, the interaction with either free or 3HNMS-occupied receptors was always characterized by the same buffer-dependent shift. Thus, even the applied rod-shaped allosteric agents do not appear to switch to the orthosteric site in free compared with orthoster-occupied M2 receptors.
The liquid‐crystalline behavior of rod‐like mesogens is normally associated with the formation of smectic layer structures. However, it is shown that the introduction of large hydrophilic groups in a ...lateral position, such as in the Figure, can lead to columnar mesophases. The formation of columnar mesophases by rod‐like molecules is suggested to be a more general phenomenon than currently thought.
Coenzyme A glutathione disulfide (CoA-SSG) was recently isolated from bovine adrenal glands and was shown to be a renal vasoconstrictor. The identification of CoA-SSG in human parathyroid glands and ...its action on cultured vascular smooth muscle cells (VSMCs) are described here.
After purification to homogeneity by several chromatographic steps, CoA-SSG was identified by matrix-assisted laser desorption/ionization mass spectrometry and enzymatic analysis. The dose-dependent growth-stimulating effect of CoA-SSG on VSMCs, measured by the (3)Hthymidine method, is characterized by a threshold of 10(-)(8) mol/L and a maximum effect of 10 micromol/L, increasing VSMC proliferation 254+/-21% above control. A dose of 10 micromol/L methylmalonyl-CoA and 10 micromol/L CoA increased the rate of proliferation of VSMCs only by 178+/-43% and 50+/-42% above control, respectively. Glutathione has no proliferative effect on VSMCs. The growth-stimulating effect of CoA-SSG (1 micromol/L) was decreased by the antagonists 3,7-dimethyl-1-propargylxanthine (DMPX; 11 micromol/L) (38% compared with CoA-SSG without antagonist) and pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS; 10 micromol/L) (48% compared with CoA-SSG without antagonist; each P:<0. 05 versus control), indicating that the effect is mediated partly via A(2) and partly via P(2)Y(1) and/or P(2)Y(4) receptor.
CoA-SSG may play a regulatory role in VSMC growth as a progression factor and thereby could play an important role in development of hypertension.
The polymorphic fungus Candida albicans can live as an aggressive pathogen that causes a wide variety of diseases in humans. Host resistance against these infections is mediated predominantly by ...phagocytes, namely neutrophils and macrophages. This report provides two game theoretical models of ingested Candida albicans cells in macrophages. Two strategies are available for each pathogenic yeast cell: avoiding lysis transiently (called silencing) or forming hyphae and escaping (called piercing because the macrophage is pierced from inside). In dependence on parameter values, two different outcomes can be derived from the model: when the difference of the costs of the two strategies is low, all fungal cells inside a macrophage will play the piercing strategy, while in the high-cost case, a mixed population of piercing and silencing cells is the only stable solution. Further, the role of the SAP gene family encoding secreted proteinases and the Sap proteins is investigated with the help of known studies and is put in relation to the costs of the strategies, the most important parameter of this model. Our results are in agreement with wet-lab results presented by other groups and the model parameters can be estimated from experimental data.
The diagnosis of movement disorders and the distinction between their possible generation by drug-treatment or illness can be done more objectively by using digitized analyses of hand movements. The ...aim of this study was to define this method, that is to identify its reliability and the influence of several covariables upon measurements, in healthy subjects. Simple writing and drawing tests were administered, using a digitizing tablet, transmitting signals to a computer for processing. The kinematic parameters identified in this way provided objective, reliable and valid measures for the dynamics and the degree of automation of hand movements. Analysis of the data showed that younger subjects write faster and with a higher degree of automation than older subjects. Other moderating variables, such as verbal intelligence and customary motor activity in everyday life (motoric practice) could be identified, whereas personality and gender were found to have little influence. There were no significant differences between left-handers and right-handers in hand movements. The movement parameters had a high test–retest stability. The results of this study in healthy subjects indicate that age, verbal intelligence and motor practice should be considered when evaluating the effects of drug-treatment or psychiatric illness upon hand-movement in patients.
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