[Long-term follow-up of psychogenic pseudosyncope]. / Het beloop van psychogene pseudosyncope na meedelen van de diagnose.

BACKGROUND: Patients with psychogenic pseudosyncope (PPS) are frequently seen by neurologists and psychiatrists. As of yet, there has been no follow-up study of patients with PPS after communicating the diagnosis. AIM: To determine the outcome of patients with psychogenic pseudosyncope (PPS) after communicatingthe diagnosis. METHOD: A retrospective cohort study of patients with PPS referred to a tertiary referral center for syncope from 2007 to 2015. We reviewed patient records, studying attack frequency, factors possibly affecting attack frequency, health care use and quality of life using questionnaires. We explored influences on absence of attack and attack frequency in the six months before follow-up for age, sex, level of education, duration until a diagnosis was made, probability of diagnosis, additional syncope and acceptance of diagnosis. RESULTS: 47 out 57 PPS cases could be traced, of these 35 (74%) participated. Twelve (34%) were attack free for at least six months. The median time from diagnosis to follow-up was 50 months (range 6-103 months). Communication and explanation of the diagnosis resulted in immediate reduction of attack frequency (p=0.007) from the month before diagnosis (median one attack, range 0-156) to the month afterwards (median one attack, range 0-16). In the six months before follow-up the number of admissions decreased from 19/35 to 0/35 (p = 0.002). Furthermore, the demand for somatic health care shifted to psychiatric care (p < 0.0001). Quality of life at follow-up (Short Form Health Survey 36; SF-36) showed lower scores for seven of the eight domains compared to matched Dutch control values. The quality of life was not significantly influenced by absence of attack. CONCLUSION: After communicating the diagnosis of PPS, attack frequency decreased and health care use shifted toward mental care. Low quality of life underlines the fact that PPS is a serious condition. Improvement of quality of life probably requires both a longer treatment and longer follow-up.

Tilt table testing in neurology and clinical neurophysiology.

Reflex syncope is responsible for 1-6% of hospital admissions and the economic burden of syncope is huge. A considerable part of these high costs is still spent on tests that are not indicated. Till now few neurologists have taken an interest in syncope and tilt table testing (TTT). However, reflex syncope and epilepsy are often in each other's differential diagnosis and require a similar emphasis on history taking and deductive reasoning. A TTT can be helpful for diagnosis and treatment. The pathophysiological rationale behind the TTT is the fact that it uses gravity to provoke a downwards shift of blood that in turn triggers syncope. Various indications and methods of the TTT are discussed in this paper.

Patient satisfaction with anaesthesia - Part 1: satisfaction as part of outcome - and what satisfies patients.

Patients' involvement in all decision processes is becoming increasingly important in modern healthcare. Patient satisfaction is a sensitive measure of a well-functioning health service system. The objective of this review is to discuss patient satisfaction as part of outcome quality, to define the somewhat abstract term 'satisfaction', and to discuss the role of surrogate markers within the field of satisfaction with anaesthesia care. We critically discuss what is relevant to satisfy patients with anaesthesia care, and we provide guidance on improving satisfaction.

Patient satisfaction with anaesthesia - Part 2: construction and quality assessment of questionnaires.

The construction of a new, valid and reliable questionnaire to measure patient satisfaction is a complex and time-consuming task. It must follow a rigorous, step-by-step approach, and should as a minimum include elements of content validity, criterion validity, construct validity and reliability. The objective of this review is to present a protocol for the construction of a psychometric questionnaire, supplemented by practical aspects for researchers and clinicians.

Does a postoperative visit increase patient satisfaction with anaesthesia care?

BACKGROUND: 'Continuity of personal care by anaesthetist', as defined by a single anaesthetist providing preoperative evaluation, performing anaesthesia, and delivering a postoperative visit to the patient, has been shown to be a major factor for patient satisfaction with anaesthesia care. This prospective randomized study investigated whether a single postoperative visit increased the patient's perception of 'Continuity of personal care by anaesthetist' and hence satisfaction. METHODS: In Group 1, the same anaesthetist who conducted anaesthesia visited the patient on the first postoperative day. In Group 2, a nurse anaesthetist who did not participate in anaesthesia delivery made a postoperative visit to the patient. Patients in Group 3 were not visited. Patients received a previously validated questionnaire after discharge from hospital. RESULTS: The negative patient response created by the perception of not being visited after operation by the attending anaesthetist was 13.5% (95% CI ± 6.9), 69.2% (95% CI ± 10.3), and 77.1% (95% CI ± 9.1) in Groups 1, 2, and 3, respectively, with 1 vs 2 and 1 vs 3 (P < 0.001) being significantly different. The negative patient response for 'Continuity of personal care by anaesthetist' was 40.0% (95% CI ± 5.3), 48.8% (95% CI ± 5.6), and 55.5% (95% CI ± 5.3) in Groups 1, 2, and 3, respectively, with 1 vs 3 (P < 0.001) being significantly different. CONCLUSIONS: Perception of the anaesthetist and satisfaction with 'Continuity of personal care by anaesthetist' were significantly increased by the introduction of a single postoperative visit by the anaesthetist compared with no visit at all. Overall satisfaction with anaesthesia was unchanged.

Effect of timing on the response to postal questionnaires concerning satisfaction with anaesthesia care.

BACKGROUND: There is little information on the effect of time on the assessment by the patient of quality of anaesthesia care. This study compared the patient's assessment of anaesthesia care after three different periods of time following discharge from hospital. Materials. Three groups of patients were assigned to receive a standardized, validated psychometric questionnaire either 1, 5, or 9 weeks after discharge from hospital. We measured response rate and the total mean problem score of six dimensions. RESULTS: Groups 1, 2, and 3 received 748, 743, and 723 questionnaires, respectively. The response rates including one reminder were 67.3 (95% confidence interval [CI] 63.9-70.6%), 64.5% (CI 61.1-67.9%), and 58.9% (CI 55.5-62.4%), respectively (Group 1 vs Group 3, P<0.001, and Group 2 vs Group 3, P<0.05). The total mean problem scores were not significantly different with 17 (CI 1.4%), 17 (CI 1.4%), and 15% (CI 1.3%), respectively. In two out of six dimensions ('Continuity of personal care by anaesthetist' and 'Nursing care in recovery room') significantly less problems were reported after 9 weeks. The other dimensions of the questionnaire showed no consistent differences between groups. CONCLUSIONS: The response rate is significantly lower at 9 weeks compared with 1 and 5 weeks after discharge. The total mean problem score remains unchanged but certain fields show fewer problems after 9 weeks compared with 1 and 5 weeks. Questionnaires on patient satisfaction with anaesthesia care should be sent within 5 weeks of discharge.

Cocaine-induced potentiation of synaptic strength in dopamine neurons: behavioral correlates in GluRA(-/-) mice.

Synaptic plasticity in the mesolimbic dopamine (DA) system is thought to contribute to the neural adaptations that mediate behavioral sensitization, a model for core aspects of addiction. Recently, it has been demonstrated that multiple classes of drugs of abuse, as well as acute stress, enhance strength at excitatory synapses on midbrain DA neurons. Here, we show that both the cocaine- and stress-induced synaptic enhancement involves an up-regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This enhancement requires the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluRA as evidenced by its absence in mice lacking this subunit. The cocaine-elicited, but not the stress-elicited, synaptic potentiation in DA neurons was blocked by a D1-like receptor antagonist, indicating that the in vivo triggering mechanisms differ for these forms of experience-dependent synaptic modification. Surprisingly, behavioral sensitization to cocaine was elicited in GluRA(-/-) mice, indicating that potentiation of excitatory synaptic transmission in DA neurons is not necessary for this form of behavioral plasticity. However, GluRA(-/-) mice did not exhibit a conditioned locomotor response when placed in a context previously paired with cocaine, nor did they exhibit conditioned place preference in response to cocaine. We suggest that the drug-induced enhancement of excitatory synaptic transmission in midbrain DA neurons, although not required for behavioral sensitization per se, may contribute to the attribution of incentive value to drug-associated cues.

Manipulation of the delayed rectifier Kv1.5 potassium channel in glial cells by antisense oligodeoxynucleotides.

Glial cells have been shown to express several biophysically and pharmacology distinct potassium channel types. However, the molecular identity of most glial K+ channels is unknown. We have developed an antibody specific for the Shaker type potassium channel Kv1.5 protein, and demonstrate by immunohistochemistry the presence of this channel in glial cells of adult rat hippocampal and cerebellar slices, as well as in cultured spinal cord astrocytes. Immunoreactivity was particularly intense in the endfoot processes of astrocytes surrounding the microvasculature of the hippocampus. The specific contribution of this channel protein to the delayed rectifying K+ current of spinal cord astrocytes was determined by incubating these cells with antisense oligodeoxynucleotides complementary to the mRNA coding for Kv1.5 protein. Such treatment reduced delayed rectifier current density and shifted the potassium current steadystate inactivation, without altering current activation, cell capacitance, or cell resting potential. The tetraethylammonium acetate (TEA) sensitivity of astrocytic delayed rectifier current was enhanced following antisense oligodeoxynucleotide treatment, suggesting that Kv1.5 channel protein may provide a significant component of the TEA-insensitive current in this preparation. Our results suggest that Kv1.5 is widely expressed in glial cells of brain and spinal cord and that delayed rectifying K+ currents in astrocytes are largely mediated by Kv1.5 channel protein.

Elimination of potassium channel expression by antisense oligonucleotides in a pituitary cell line.

The clonal rat pituitary cell line GH4C1 expresses the genes for several voltage-dependent potassium channels including Kv1.5 and Kv1.4. Dexamethasone, a glucocorticoid agonist, induces a slowly inactivating potassium current in these cells but does not alter the amplitude of a rapidly inactivating component of potassium current. We have found that the induction of the slowly inactivating current can be blocked by an antisense phosphorothioate deoxyoligonucleotide to the Kv1.5 mRNA sequence. In contrast, antisense deoxyoligonucleotides against Kv1.4 mRNA specifically decrease the expression of the dexamethasone-insensitive rapidly inactivating current. These results demonstrate the usefulness of antisense oligonucleotides in correlating potassium currents with specific potassium channel proteins in the cell types in which they are naturally expressed.

Fish oil, enriched with polyunsaturated fatty acids of the omega-3-type accelerates the nucleation time in healthy subjects.

The daily administration of fish oil, containing 1.5 g omega-3-fatty acids causes a significant decrease in nucleation time (12.1 +/-7.3 vs. 2.0 +/- 1.2 days, p less than 0.001), as well as in biliary cholesterol saturation and biliary cholesterol composition in 13 healthy subjects. The nucleation time, cholesterol saturation index and biliary lipids showed no significant differences in 11 cholesterol gallstone patients after a six-week treatment period with omega-3-fatty acids. Taurocholate percentage increased significantly in the gallstone group (10.4 +/- 3.9 vs 13.5 +/- 1.7%, p less than 0.05). The levels of the other bile acids remained unchanged during the treatment period. Therefore, the incidence of gallstones might be increased after treatment with fish oil, containing omega-3-fatty acids.

[Effect of omega-3-fatty acids on biliary lipids and lithogenicity]. / Einfluss von Omega-3-Fettsäuren auf biliäre Lipide und Lithogenität.

Until now no studies are available about the influences of omega-3-fatty acids on biliary lipids in men. The effects of 1.5 g omega-3-fatty acids per day on biliary lipid concentration and composition were studied in 13 male healthy persons over six weeks. Biliary cholesterol concentration decreased from 5.4 +/- 0.53 mol% to 3.7 +/- 0.30 mol% (25%) statistically significant. Phospholipids and bile acids remained unchanged. Cholesterol saturation index (CSI) was lowered from 1.13 +/- 0.12 to 0.85 +/- 0.06 (p less than 0.05). Bile acid composition and conjugation rates were unchanged. No significant side effects could be observed. Substitution of omega-3-fatty acids induced in healthy male persons a decrease of biliary cholesterol and lithogenicity.

Effects of 5-fluorouracil/guanine wobble base pairs in Z-DNA: molecular and crystal structure of d(CGCGFG).

The chemotherapeutic agent 5-fluorouracil is a DNA base analogue which is known to incorporate into DNA in vivo. We have solved the structure of the oligonucleotide d(CGCGFG), where F is 5-fluorouracil (5FU). The DNA hexamer crystallizes in the Z-DNA conformation at two pH values with the 5FU forming a wobble base pair with guanine in both crystal forms. No evidence of the enol or ionized form of 5FU is found under either condition. The crystals diffracted X-rays to a resolution of 1.5 A and their structures have been refined to R-factors of 20.0% and 17.2%, respectively, for the pH = 7.0 and pH = 9.0 forms. By comparing this structure to that of d(CGCGCG) and d(CGCGTG), we were able to demonstrate that the backbone conformation of d(CGCGFG) is similar to that of the archetypal Z-DNA. The two F-G wobble base pairs in the duplex are structurally similar to the T-G base pairs both with respect to the DNA helix itself and its interactions with solvent molecules. In both cases water molecules associated with the wobble base pairs bridge between the bases and stabilize the structure. The fluorine in the 5FU base is hydrophobic and is not hydrogen bonded to any solvent molecules.

Intracardiac extension of intravenous leiomyomatosis.

A 42-year-old woman was found to have intravenous leiomyomatosis of the uterus with extension into the inferior vena cava and right atrium. Intravenous leiomyomatosis is a rare neoplastic disease characterized by invasion of venous channels by a benign smooth muscle tumor arising either from the wall of a vessel or from a uterine myoma. Intracardiac extension is often initially misdiagnosed as a right atrial myxoma and may cause death by mechanical obstruction. The diagnosis of intravenous leiomyomatosis should be considered in young women with cardiac symptoms associated with a right atrial mass who also have a pelvic mass or who have previously undergone hysterectomy because of leiomyoma uteri.

The interactions of ruthenium hexaammine with Z-DNA: crystal structure of a Ru(NH3)6+3 salt of d(CGCGCG) at 1.2 A resolution.

A crystal of d(CGCGCG) in the Z-DNA lattice was soaked with ruthenium(III) hexaammine and its structure refined at 1.2 A resolution. Three unique metal complexes were found absorbed to each hexamer duplex. In addition, two symmetry-related binding sites were located, yielding a total of five ruthenium complexes bound to each d(CGCGCG) duplex. One unique site and its symmetry related site are nearly identical to the binding site of cobalt(III) hexaammine on Z-DNA. At that position, the metal complex bridges the convex surfaces of two adjacent Z-DNA strands by hydrogen bonds to the N7 and O6 functional groups of the guanine bases. The remaining three ruthenium three ruthenium(III) hexaammine binding sites are not present in the cobalt(III) hexaammine Z-DNA structure. Of these, two are related by symmetry and span the gap between the convex outer surface of one Z-DNA strand and the helical groove crevice of a neighboring strand. The third ruthenium site has no symmetry mate and involves interactions with only the deep groove. In this interaction, the metal complex hydrogen bonds to both the phosphate backbone and to a set of primary shell water molecules that extend the hydrogen bonding potential of the deep groove crevice out to the surface of the molecule. Solution studies comparing the circular dichroism spectra of low salt poly(dG-dC).poly(dG-dC) samples in the presence of ruthenium(III) and cobalt(III) hexammine show that the ruthenium complex does stabilize Z-DNA in solution, but not as effectively as the cobalt analogue. This suggests that some of the interactions available for the larger ruthenium complex may not be important for stabilization of the left-handed DNA conformation.