Memory and metamemory in schizophrenia: a liberal acceptance account of psychosis.

BACKGROUND: In previous studies we suggested that liberal acceptance (LA) represents a fundamental cognitive bias in schizophrenia and may explain why patients are more willing to accept weak response alternatives and display overconfidence in incorrect responses. The aim of the present study was to test a central assumption of the LA account: false alarms in schizophrenia should be particularly increased when the distractor-target resemblance is weak relative to a control group. METHOD: Sixty-eight schizophrenia patients were compared to 25 healthy controls on a visual memory task. At encoding, participants studied eight complex displays, each consisting of a unique pairing of four stimulus attributes: symbol, shape, position and colour. At recognition, studied items were presented along with distractors that resembled the targets to varying degrees (i.e. the match between distractors and targets ranged from one to three attributes). Participants were required to make old/new judgements graded for confidence. RESULTS: The hypotheses were confirmed: false recognition was increased for patients compared to controls for weakly and moderately related distractors only, whereas strong lure items induced similar levels of false recognition for both groups. In accordance with prior research, patients displayed a significantly reduced confidence gap and enhanced knowledge corruption compared to controls. Finally, higher neuroleptic dosage was related to a decreased number of high-confident ratings. CONCLUSIONS: These data assert that LA is a core mechanism contributing to both enhanced acceptance of weakly supported response alternatives and metamemory deficits, and this may be linked to the emergence of positive symptomatology.

The structure of the fibrous tissue on the articular surface of the temporal bone in the monkey (Macaca mulatta).

The articulating surface of bones which ossify in mesenchyme, like the mandible, is covered by a layer of dense, fibrous tissue. The purpose of the present study was to examine the structure of the fibrous tissue on the surface of the articular surface of the temporal bone in the monkey. Young Rhesus monkeys (Macaca mulatta) were perfused with glutaraldehyde-paraformaldehyde. The specimens were demineralized in 0.5M EDTA. Small pieces of fibrous tissue and underlying bone were dissected out and processed for light and electron microscopy. The mandibular fossa is shallower and the articular eminence flatter in the monkeys as compared to humans. The articular part of the temporal bone is covered by a layer of avascular, soft tissue extending from the surface to the underlying bone. The tissue can be divided into three zones which gradually merge into one another. The zone facing the articular cavity consists of dense, fibrous tissue with layers of collagen fibers, oriented parallel to the articular surface, but at angles to each other. Fibers thought to be elastic fibers oriented parallel with the collagen fibers are also observed, particularly close to the surface, and their function is probably to impart resilience to the fibrous articular tissue. Between the fibers scattered cells with an ample rough endoplasmic reticulum are present. A thin layer of granular appearance is often observed on the surface. This layer may be of importance in joint lubrication. The second zone is more cell rich and the cells have long slender cellular processes and are surrounded by a dense collagenous matrix with an irregular orientation. These cells are probably precursor for the underlying cartilage but, not for the cells in the outer articular layer. In the third zone next to the bone the fibrous tissue gradually turns into cartilage. The cartilagenous zone is narrow, sometimes absent and is replaced by bone tissue. In some areas chondroclasts are observed, with forming osteons with osteoid seams. These observations indicate that remodeling is taking place and that cartilage is replaced by bone. The three zones observed correspond to findings in the mandibular condyle, but the zones are not as constant and distinct as in the condyle, and this reflects the adaptive role of the temporal bone in the growth of the temporomandibular joint.

Further observations on tertiary dentin in human deciduous teeth.

The structure of reparative tertiary dentin in human deciduous teeth has been studied. Reparative dentin is secreted by a new generation of odontoblast-like cells which have been subject to strong stimuli, e.g., trauma or deep active caries lesions with associated pulp inflammation. Ground sections of 25 teeth were prepared, and contact microradiographs were produced. Another 30 teeth were demineralized, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Some demineralized sections from each tooth were also studied in the scanning electron microscope. Most of the teeth showed some type of tertiary dentin formation. Mineralized tissue with a varied morphology was observed. In teeth which had been subject to trauma, the entire pulp chamber was sometimes obliterated. Mineralization seemed to start in the incisal region, and the central part of the pulp was the last part to be obliterated. Radiolucent voids and canals were seen. The organic matrix was dense and fibrous. In the pulp chamber and especially in the root canals, resorption had often occurred, indicating that signals giving rise to odontoclasts were also present. Resorption was often followed by deposition of various amounts of cementum-like repair tissue. The cells responsible for the formation of reparative dentin are believed to be subodontoblasts or undifferentiated ectomesenchymal cells. The varied morphology of the reparative dentin, observed in the pulp of the teeth examined, indicates that different stimuli lead to induction of hard-tissue-forming cells which produce different types of hard tissue.

Contrasting cardiac regional responses of A-type and B-type natriuretic peptide to experimental chronic heart failure.

OBJECTIVE: The aim of this study was to examine the regional myocardial variation in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) synthesis during development of congestive heart failure (CHF). METHODS: Heart failure was induced by left atrial rapid pacing for 3 weeks in pigs. The gene expression of ANP and BNP was measured by northern blot analysis and the peptide concentration in myocardial tissue and plasma by radioimmunoassay (RIA). RESULTS: At the end of the pacing period pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) increased, and cardiac output (CO) decreased compared to sham-operated controls (PCWP: 17.6 +/- 1.9 vs. 3.1 +/- 0.9 mmHg) (RAP: 10.4 +/- 1.7 vs. 2.2 +/- 0.6 mmHg) (CO: 3.5 +/- 0.4 vs. 5.3 +/- 0.3 l/min), indicating a state of moderate to severe CHF. The gene expression and tissue concentration of BNP was low in sham pigs, but was strongly increased in all cardiac regions, and especially in the left ventricle, during CHF. In contrast, ANP was mainly produced in the atria both in normal and heart failure conditions. The relative increases in mRNA levels, tissue concentrations and circulating peptide concentrations were more profound for BNP than for ANP. CONCLUSIONS: In response to CHF induction, ANP and BNP respond differently across the cardiac regions. Strong expression of the BNP gene was only found in the heart failure state, while ANP was clearly expressed also in the normal state. These findings support the concept of BNP being superior to ANP as a biochemical marker of CHF.

Cardiac natriuretic peptides and continuously monitored atrial pressures during chronic rapid pacing in pigs.

Changes in atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide and brain natriuretic peptide (BNP) were evaluated in relation to continuously monitored atrial pressures in a pacing model of heart failure. Pigs were subjected to rapid atrial pacing (225 beats min-1) for 3 weeks with adjustments of pacing frequencies if the pigs showed overt signs of cardiac decompensation. Atrial pressures were monitored by a telemetry system with the animals unsedated and freely moving. Left atrial pressure responded stronger and more rapidly to the initiation of pacing and to alterations in the rate of pacing than right atrial pressure. Plasma natriuretic peptide levels were measured by radioimmunoassay and all increased during pacing with BNP exhibiting the largest relative increase (2.9-fold increase relative to sham pigs). Multiple regression analysis with dummy variables was used to evaluate the relative changes in natriuretic peptides and atrial pressures and the strongest correlation was found between BNP and left atrial pressure with R 2=0.81. Termination of pacing resulted in rapid normalization of ANP values in spite of persistent elevations in atrial pressures. This may reflect an increased metabolism or an attenuated secretory response of ANP to atrial stretch with established heart failure. In conclusion, 3 weeks of rapid pacing induced significant increases in atrial pressures and natriuretic peptide levels. All the natriuretic peptides correlated with atrial pressures with BNP appearing as a more sensitive marker of cardiac filling pressures than ANP and N-terminal proatrial natriuretic peptide.

Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF.

Endothelin (ET) contributes to the increased systemic vascular resistance and elevated cardiac filling pressures seen in congestive heart failure (CHF). We investigated to what extent ET-mediated vasoconstriction in CHF occurs through an endocrine action of elevated plasma ET or by an autocrine/paracrine mechanism related to induction of vascular ET gene expression. Three weeks of pacing (225 beats/min) induced a marked release of ET-1 from the pulmonary circulation with a sixfold elevation of arterial plasma ET in CHF pigs compared with sham-operated pigs. Arterial plasma ET was the strongest and only independent predictor of systemic vascular resistance. In contrast, vascular preproET-1 and ET-receptor mRNA expression were unaltered or decreased in CHF pigs and did not correlate with indexes of vascular tone. However, myocardial preproET-1 mRNA expression increased twofold in CHF pigs. PreproET-2 and preproET-3 mRNAs were not detectable in cardiovascular tissues. In conclusion, plasma ET was markedly increased because of an augmented release from the pulmonary circulation during CHF, and arterial plasma ET correlated with systemic vascular resistance. The absence of ET induction in the peripheral vasculature suggests that ET increases vascular tone during CHF by an endocrine, not an autocrine/paracrine, mechanism.

A microradiographic and electron microscopic study of tertiary dentin in human deciduous teeth.

This study deals with the structure of the inorganic phase of tertiary dentin, and is limited to dentin formation caused by mild or moderate stimuli, e.g., attrition or initial or shallow carious lesions. Ground sections were prepared from 20 human deciduous teeth extracted mainly because of orthodontic treatment, and contact microradiographs were produced. Based on visual inspection of the ground sections in reflected and transmitted light and microradiographic findings, small areas were dissected out and processed for electron microscopy. In the tertiary dentin formed in the pulp horns the number of tubules was reduced, while in that on the side walls of the pulp there was often no marked reduction in the number of tubules. Several tubules could be followed from the physiological (primary and secondary) dentin into the tertiary dentin, and a change in the direction of the tubules was often noted. Interglobular dentin was frequently observed, and in some teeth incremental lines with alternating high and low mineral content were seen, indicating that tertiary dentin, like other mineralized tissues, is subject to biological rhythms during formation. When studied in the electron microscope, tubules with varying size and distribution as well as occluded tubules with a high mineral content were seen. The tubules often had an irregular circumference with projections of mineralized tissue protruding into the lumen. Highly mineralized peritubular dentin was rarely observed. The present results show that orthodentin is formed when dentin in primary human teeth is exposed to mild or moderate stimuli.

N-terminal proatrial natriuretic peptide in angina pectoris: impact of revascularization by angioplasty.

AIMS: We investigated whether levels of N-terminal proatrial natriuretic peptide (N-terminal proANP) reflect the severity of coronary artery disease in chronic, stable angina pectoris. Furthermore, we investigated if revascularization by percutaneous transluminal coronary angioplasty (PTCA) affected the N-terminal proANP level and, finally, whether restenosis could be predicted by changes in N-terminal proANP after PTCA. METHODS AND RESULTS: N-terminal proANP was measured in 286 patients before and after PTCA. The patients' baseline level of N-terminal proANP (787+/-403 pmol/l) correlated significantly with left ventricular end diastolic pressure, age and serum creatinine, but not with the number of stenotic vessels. Twenty-four hours post-PTCA N-terminal proANP decreased significantly, and completely revascularized patients demonstrated a decline two-fold larger than those incompletely revascularized (deltaN-terminal proANP -114+/-178 vs. -53+/-231 pmol/l, P<0.05). After 14 days N-terminal proANP had returned to baseline in both groups. Changes in N-terminal proANP from post-PTCA to the final follow-up was not predictive of angiographic restenosis. INTERPRETATION: The significant decrease in N-terminal proANP observed after angioplasty, most pronounced in patients completely revascularized, is thought to reflect a transient improvement in resting left ventricular function.

An experimental study of cardiac natriuretic peptides as markers of development of congestive heart failure.

The use of cardiac peptide measurements as possible diagnostic tools in congestive heart failure has been extensively discussed in the recent literature. Therefore, the aim of this study was to establish a model of experimental chronic heart failure, and thereby perform a comparative study of secretion and circulating levels of the cardiac peptides atrial natriuretic peptide (ANP), N-terminal proatrial natriuretic peptide (N-terminal proANP) and brain natriuretic peptide (BNP) during evolving heart failure. Chronic heart failure was induced in seven pigs by rapid left atrial pacing for three weeks. The effects of failure induction were documented 24 h after pacemaker deactivation. Hemodynamic indices of cardiac preload, like pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP), were all considerably increased compared to sham operated controls. Likewise, plasma endothelin-L, noradrenaline, renin activity, aldosterone and angiotensin II were all markedly increased. Heart failure was accompanied by significant increases in both estimated cardiac secretory rate and plasma concentrations of all three cardiac peptides, significantly correlated to the PCWP. The directional changes during evolving heart failure were similar, although the percentage increase in plasma BNP was much larger than for ANP and N-terminal proANP. In absolute molar terms, however, the BNP concentration changes were minor compared to those of the other two peptides. The larger percentage increase of BNP might indicate its superiority as a marker of heart failure development, provided a functional assay suitable for clinical use can be designed for a peptide circulating in this low concentration range.

Effects of angiotensin II receptor blockade on N-terminal proatrial natriuretic factor plasma levels in chronic heart failure.

BACKGROUND: Plasma N-terminal proatrial natriuretic factor (N-terminal proANF) has been shown to reflect intraatrial pressures in heart failure patients, and may be used as a biochemical parameter of atrial pressures. It is still unclear how treatment of heart failure influences the relationship between hemodynamic parameters and plasma levels of N-terminal proANF. METHODS AND RESULTS: This double-blind, placebo-controlled study investigated whether 12 weeks of treatment with the angiotensin II receptor blocker losartan influenced N-terminal proANF plasma levels in 129 chronic heart failure patients. After 12 weeks of treatment, N-terminal proANF level was increased in patients given placebo by 344 +/- 1126 pmol/L, whereas in patients given 50 mg losartan, the levels had decreased by 251 +/- 886 pmol/L (P < .01 vs placebo). The change in N-terminal proANF correlated significantly with the corresponding change in pulmonary capillary wedge pressure (r = .53, P < .001). CONCLUSION: The correlation between N-terminal proANF plasma levels and pulmonary capillary wedge pressure at baseline, as well as the correlation between the changes in these parameters during treatment, suggests that plasma N-terminal proANF may be used to monitor effects on left ventricular filling pressures in patients treated with losartan.

Cardiac secretion of atrial and brain natriuretic peptides in acute ischaemic heart failure in pigs: effect of angiotensin II receptor antagonism.

In a model of acute ischaemic left ventricular failure in pigs, we compared the plasma levels and cardiac secretion of the three atrial peptides, atrial natriuretic factor (ANF), N-terminal proatrial natriuretic factor (N-terminal proANF) and brain natriuretic peptide (BNP). Acute ischaemic left ventricular failure was induced by embolization of the left coronary artery with plastic microspheres. Thereafter, treatment was given by an intravenous injection of the angiotensin II receptor (AT1) antagonist losartan. Effects of failure induction and treatment were documented by measurement of haemodynamic parameters and plasma concentrations of catecholamines, plasma renin activity, angiotensin II and aldosterone. Acute left ventricular failure was accompanied by significant increases in cardiac secretion and plasma levels of all three atrial peptides, which was considerably more pronounced for ANF and N-terminal proANF than for BNP. Treatment with losartan resulted in significant decreases in plasma ANF and N-terminal proANF, whereas BNP did not change. These findings indicate that ANF and N-terminal proANF may be better suited than BNP as markers of cardiac preload during the development and treatment of acute heart failure.

The structure of the mandibular condyle in the monkey (Macaca mulatta).

The articulating surfaces of bones which ossify in mesenchyme, like the mandible, are covered by a layer of dense, fibrous tissue. The purpose of the present study was to examine the structure of the mandibular condyle in the monkey. Young Rhesus monkeys (Macaca mulatta) were perfused with glutaraldehyde-paraformaldehyde. Small pieces of the condyles were dissected out, demineralized in 0.5 M EDTA and processed for light microscopy and electron microscopy. The mandibular condyle was covered by an avascular tissue, extending from the surface to the underlying bone. The tissue could be divided into three zones. The zone facing the articular cavity was about 50 microns wide and consisted of a dense, fibrous tissue. Layers of collagen fibers, 1-4SS microns wide and parallel with the articular surface, but oriented at angles to each other, were seen. Between the collagen fibers fibroblast-like cells were noted. The second zone was also approximately 50 microns wide and rich in cells. The cells were ovoid or flat and had a dark staining cytoplasm with some mitochondria and a well developed rough-surfaced endoplasmic reticulum. The third zone was about 150 microns wide and here the cells were larger and located in lacunae. An increase in the size of cells and lacunae was seen approaching the bone. This zone showed hyaline cartilage undergoing maturation. Closer to the bone, degeneration of the chondrocytes was noted. In the underlying bone, soft tissue with several chondroclasts resorbing the hypertrophic cartilage were seen, alternating with areas where bone formation was occurring, partly on the top of cartilage remnants. The observations confirm that in the growing condyle there is an articular part as well as a growth zone, and that the cells in the cell-rich zone serve as precursors for the hyaline cartilage cells in the growth zone, and possibly as a cell reservoir for the articular part as well.

The ultrastructure of copper amalgam-covered dentin from human deciduous teeth.

The structure of dentin subjacent to Cu-amalgam restorations was studied. The restorations had been inserted 7-8 years before extraction of the teeth. No lining had been applied. The dentin subjacent to the restorations had a greenish-grayish discoloration, and in the pulpal end irregular secondary dentin had formed. Energy-dispersive X-ray microanalysis of areas showing discoloration confirmed the presence of Cu. Semithin and ultrathin undemineralized sections were studied. Vital pulp tissue and irregular secondary dentin were observed. Close to the predentin and halfway into the dentin most of the dentinal tubules were occluded. In the control material only an occasional occluded tubule was seen. Close to the Cu-amalgam restoration some tubules were occluded or partly occluded, and some were open. The odontoblasts had responded to the irritating agent by obturation of the tubules, thus reducing the permeability of the dentin. Furthermore, irregular secondary dentin had formed in another attempt to wall off the irritating agent.

[Axis divergence in electrocardiography as a sign of heart disease]. / Die Achsendivergenz im Ekg als Zeichen einer Herzerkrankung

In the ecgs of 3433 patients the QRS- and T-vectors were determined. The borderline between physiological and pathological ranges of axis-divergence is found to show fluctuations. The younger the patient and the steeper the electrical heart axis, the greater is the physiological axis-divergence. Ignoring this fact many young people by mistake are taken to suffer from a cardiac disease on account of a great axis-divergence. On the other hand the same setting often is the only sign of a heart disease. The axis-divergence can be a useful factor for the computer-analyzed ecg, although the evaluation of a tenfold of ecgs seems to be necessary to achieve a statistically significant statement.