Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects.

MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, pBonferroni = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort.

Sex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals. Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, undergoing GHT, and 15 age-matched cisgender women (CW), receiving no therapy, underwent MRSI before and after at least 12 weeks. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (combination of GABA and macromolecules) and Glx (combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus). Linear mixed models analysis revealed a significant measurement by gender identity effect (pcorr. = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (pcorr. = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men. Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies. DATA AVAILABILITY STATEMENT: Due to data protection laws processed data is available from the authors upon reasonable request. Please contact rupert.lanzenberger@meduniwien.ac.at with any questions or requests.

Gender transition affects neural correlates of empathy: A resting state functional connectivity study with ultra high-field 7T MR imaging.

Sex-steroid hormones have repeatedly been shown to influence empathy, which is in turn reflected in resting state functional connectivity (rsFC). Cross-sex hormone treatment in transgender individuals provides the opportunity to examine changes to rsFC over gender transition. We aimed to investigate whether sex-steroid hormones influence rsFC patterns related to unique aspects of empathy, namely emotion recognition and description as well as emotional contagion. RsFC data was acquired with 7Tesla magnetic resonance imaging in 24 male-to-female (MtF) and 33 female-to-male (FtM) transgender individuals before treatment, in addition to 33 male- and 44 female controls. Of the transgender participants, 15 MtF and 20 FtM were additionally assessed after 4 weeks and 4 months of treatment. Empathy scores were acquired at the same time-points. MtF differed at baseline from all other groups and assimilated over the course of gender transition in a rsFC network around the supramarginal gyrus, a region central to interpersonal emotion processing. While changes to sex-steroid hormones did not correlate with rsFC in this network, a sex hormone independent association between empathy scores and rsFC was found. Our results underline that 1) MtF transgender persons demonstrate unique rsFC patterns in a network related to empathy and 2) changes within this network over gender transition are likely related to changes in emotion recognition, -description, and -contagion, and are sex-steroid hormone independent.

Monthly itraconazole versus classic homeopathy for the treatment of recurrent vulvovaginal candidiasis: a randomised trial.

OBJECTIVE: Antimycotics effectively treat sporadic and recurrent vulvovaginal candidiasis (RVVC). Classic homeopathy (CH) is also used to treat this condition. We compared the efficacy of CH and itraconazole in reducing the frequency of RVVC episodes. DESIGN: Single-centre, prospective, randomised trial. SAMPLE: One hundred-and-fifty patients with a history of RVVC and an acute episode of VVC. METHODS: Women were randomised into 3 groups: itraconazole with lactobacilli (group 1), itraconazole without lactobacilli (group 2) and CH (group 3). Itraconazole treatment of acute infection was followed by a 6-month maintenance regimen with monthly single-day itraconazole (200 mg bid). Women in group 1 were given additional vaginal lactobacilli for 6 days per month throughout the maintenance regimen Thereafter, patients were followed without treatment for 6 months. CH treatment was performed for 12 months. RESULTS: Women in groups 1 and 2 reached a culture-free status significantly earlier than women in group 3 (log-rank test; P < 0.0001). Specifically, before the start of the maintenance regimen, 44 of 49 women (89.8%) in group 1 and 40 of 47 women (85%) in group 2 were free of Candida detectable by culture, 22 of 46 (47%) women in group 3 reached a culture-free status after the first visit, but had a recurrence significantly earlier compared with women in groups 1 and 2 (log-rank test; P = 0.002). After 12 months, 19 of 25 (76%) women in group 1, 18 of 23 (78%) women in group 2 and 9 of 23 (39%) women in group 3 were free of culture-detectable Candida. Assessment of RVVC-associated complaints by VAS score showed that women in group 3 had a significantly higher level of discomfort (36.8, 25.1 and 27.7 respectively; P < 0.001) and were significantly less satisfied (59.2, 68.2 and 71.7 respectively; P < 0.001) than patients in groups 1 and 2. CONCLUSIONS: Monthly cycle-dependent itraconazole is more effective than CH in the treatment of RVVC. Lactobacilli do not confer an added benefit.

Neural associative memories for the integration of language, vision and action in an autonomous agent.

Language understanding is a long-standing problem in computer science. However, the human brain is capable of processing complex languages with seemingly no difficulties. This paper shows a model for language understanding using biologically plausible neural networks composed of associative memories. The model is able to deal with ambiguities on the single word and grammatical level. The language system is embedded into a robot in order to demonstrate the correct semantical understanding of the input sentences by letting the robot perform corresponding actions. For that purpose, a simple neural action planning system has been combined with neural networks for visual object recognition and visual attention control mechanisms.

Activation of caspase-like activity and poly (ADP-ribose) polymerase degradation during sporulation in Aspergillus nidulans.

Mycelium vacuolization, protein degradation, and as the final stage autolysis, often accompanies developmental changes in fungi and similarities between autolysis and apoptosis have previously been suggested. Caspases are the key executors of apoptosis and in this study caspase-like activities were detected in protein extracts from Aspergillus nidulans during sporulation. This was shown by hydrolysis of the fluorescent DEVD- and IETD-AFC peptide substrates specific for caspase 3- and 8-like activities, respectively. These activities were repressed by the caspase 3 and 8 specific irreversible peptide inhibitors DEVD-fmk and IETD-fmk, but were not affected by the unspecific inhibitor E-64. Isoelectric focusing of protein extracts followed by activity staining revealed the presence of two bands with caspase-like activity. One of the proteins degraded both caspase 3 and caspase 8 specific substrates whereas the other only degraded the caspase 8 substrate. Searches in an A. nidulans genome database revealed two genes encoding metacaspase proteins with predicted sizes of 45 kDa that could be responsible for the measured caspase-like activities. The searches also found a single gene encoding a poly (ADP-ribose) polymerase (PARP) protein with a predicted size of 81 kDa. PARP is one of the known target proteins inactivated by caspase degradation in animal cells. Western blotting of fungal extracts using a bovine PARP antibody confirmed the presence of a fungal PARP-like protein of about 81 kDa. By Western blotting it was shown that this PARP-like protein band was present only at early time points until the start of conidia formation and the accompanying increase in caspase-like activity. Thereafter, a degradation product of about 60 kDa appeared indicating that the degradation of the fungal PARP-like protein was specific. The PARP antibody also recognized an 85 kDa protein band that was not degraded, and which conceivably represents a modified form of the 81 kDa PARP. Fungal extracts high in caspase-like activity could degrade both the fungal 81 kDa PARP and bovine PARP. In the presence of the caspase 3 inhibitor DEVD-fmk this degradation was delayed. Thus, as in animal apoptotic cells, caspase activities are involved in fungal mycelium self-activated proteolysis.

Seasonal and diel activity of Ixodes ricinus (Acari: Ixodidae) subpopulations in Denmark. Aspects of size, physiological age, and malate dehydrogenase genotype in a forest site without any undergrowth.

UNLABELLED: The underlying population dynamics and the behavioural patterns of the vectors are key issues in understanding the transmission of vector borne pathogens. For the tick Ixodes ricinus both seasonal and diel activity have been described as bimodal patterns, which in seasonal aspect has been interpreted as representing two cohorts. However, recent studies have shown that this interpretation may be incorrect. The aim of this study was to obtain more detailed information on nymph host seeking by studying subpopulations of ticks during the day and season. The study was designed to allow for comparisons of the diel variation and seasonal variation in their dependency in a number of tick characteristics. The study took place in a forest with planted beech trees without any undergrowth. Ticks were collected by flagging the dead leaves on the forest floor. For each nymph, a number of visual observations were made. The size and physiological age was observed and the nymphs were genotyped in the malate dehydrogenase locus (MDH, E.C. 1.1.1.37). Briefly the main results can be given as: (i) There were significant differences in the composition of size classes during the season, but only limited trends in time. (ii) The proportion of the small nymphs was highly variable, with a variation from 3% to 24% in October and September, respectively. (iii) The diel variation in MDH genotypes was significant in May and August. (iv) Nymph size classes and physiological age appeared to interact. The non-random interaction was caused by a relatively even distribution of small nymphs in all four age classes, while large nymphs tended to fall into age class 2 and 3. The length by age interaction for the individual months was noted to be significant in May, July, August and September, but not in June. Similarly the interaction was significant in the morning and afternoon, but not at midday. The overall results describe the seasonal and diel activity patterns as changing systematically for several characteristics under the influence of weather condition and population dynamics. IN CONCLUSION: The observations are best interpreted as being produced of a single cohort of ticks, but the revealed complexity of the host seeking activity suggest that measures of activity x abundance should be interpreted very cautiously in relation to population dynamics.

[Detection of the genotypic heterogeneity of Ixodes persulcatus Schulze (Acari: Ixodidae) of the North-West region of Russia and characteristics of distribution of tick-borne pathogens causing Lyme disease and Ehrlichia infections in various genotypes]. / Vyiavlenie genotipicheskoi neodnorodnosti populiatsii Ixodes persulcatus Schulze (Acari: Ixodidae) Severo-Zapada Rossii i osobennosti raspredeleniia kleshchevykh patogenov--vozbuditelei bolezni Laima i érlikhiozov v razlichnykh genotipakh.

The heterogeneity of the Ixodes persulcatus population in the vicinity of Saint Petersburg was estimated by using malate dehydrogenase (MDH) isoenzyme. There are six MDH genotypes carrying 3 alleles in the Ixodes persulcatus population. The prevalence of Borrelia and Ehrlichia species in the study genotypes was analyzed. There was a difference in the prevalence and intensity of infection. The greatest abundance of Borrelia was described in the genotypes to Genogroup 1 (with allele 1). Among them, heterozygous ticks were most intensively infected. Polymerase chain reaction identified species pathogenic for man. These included 3 species of Borrelia: B. afzelii, B. garinii, and B. burgdorferi sensu stricto and 2 species of Ehrlichia muris and HGE agent. The author are the first to describe HGE agent and B. burgdorfei ss encountered in Russia.

[Scoring multiple organ failure after severe trauma. Comparison of the Goris, Marshall and Moore scores]. / Scoring des Multiorganversagens nach schwerem Trauma. Vergleich des Goris-, Marshall- und Moore-Scores.

INTRODUCTION: MOF scores are used to predict, describe and define organ failure. The aim of this study was to compare MOF scoring systems regarding their precision. METHODS: Data on the ICU course of 301 severely injured patients (PTS > 20, age > 16 years) were documented daily for calculation of three MOF Scores (Goris, Moore, Marshall) for 14 days. Every day the patients were graded by clinical criteria into a group with and a group without MOF by an experienced intensive care physician. The cut-off point for MOF was determined by ROC analysis for each score; the sensitivity and specificity were calculated. RESULTS: The patients were 36.3 +/- 1.0 years old, the mean injury severity was 36.2 +/- 0.7 points according to the PTS. Forty-seven (15.6%) of all patients died 17.7 +/- 5.6 days after trauma. The MOF incidence was 26.1%, the MOF mortality 58.4%. The calculated cut-off point for MOF was more than 4 points for the Goris and Marshall scores and more than 3 points for the Moore score. The Moore score is, with sensitivity of 81% and specificity of 88%, superior to the other scores. The Moore score identified 93 patients (30.9%) for MOF; this corresponds with a right answer in 85%. The lower specificity of the Goris and Marshall scores was due to the judgement of liver (GOT) and cardiovascular (PAH) dysfunction respectively. CONCLUSION: For evaluation of MOF after severe trauma the Moore score is superior to other scoring systems (sensitivity 81%; specificity 87%). A score of more than 3 points is associated with MOF. The Moore score did not consider distinct parameters (S-GOT, PAH) which are included in the other systems and were of little importance in our calculations.

A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.

OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.

The armadillo repeat region targets ARVCF to cadherin-based cellular junctions.

The cytoplasmic domain of the transmembrane protein M-cadherin is involved in anchoring cytoskeletal elements to the plasma membrane at cell-cell contact sites. Several members of the armadillo repeat protein family mediate this linkage. We show here that ARVCF, a member of the p120 (ctn) subfamily, is a ligand for the cytoplasmic domain of M-cadherin, and characterize the regions involved in this interaction in detail. Complex formation in an in vivo environment was demonstrated in (1) yeast two-hybrid screens, using a cDNA library from differentiating skeletal muscle and part of the cytoplasmic M-cadherin tail as a bait, and (2) mammalian cells, using a novel experimental system, the MOM recruitment assay. Immunoprecipitation and in vitro binding assays confirmed this interaction. Ectopically expressed EGFP-ARVCF-C11, an N-terminal truncated fragment, targets to junctional structures in epithelial MCF7 cells and cardiomyocytes, where it colocalizes with the respective cadherins, beta-catenin and p120 (ctn). Hence, the N terminus of ARVCF is not required for junctional localization. In contrast, deletion of the four N-terminal armadillo repeats abolishes this ability in cardiomyocytes. Detailed mutational analysis revealed the armadillo repeat region of ARVCF as sufficient and necessary for interaction with the 55 membrane-proximal amino acids of the M-cadherin tail.

Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

Diurnal activity of Ixodes ricinus in Denmark: aspects of physiological age and genotypic variation.

Four different alleles in the nymphal Ixodes ricinus were found for the Malate Dehydrogenase enzyme (MDH). The allele frequency of the MDH genotypes in nymphal I. ricinus was observed to change during the day. Some genotypes were present in the morning, but not in the afternoon and evening. The physiological age of the nymphs was also determined. No significant correlation could be found between physiological age and genotypes. Based on the results it must be anticipated that the comparability of tick samples not only differs in quantity but also in quality for various hours, but not necessarily for various months. Therefore isoenzyme analysis of nymphs at least as regards the MDH alleles appears to be a convenient biological tool to analyse differences in host seeking behaviour.

Importance of dural ectasia in phenotypic assessment of Marfan's syndrome.

BACKGROUND: Early identification of Marfan's syndrome is fundamental in the prevention of aortic dilatation, but the wide phenotypic expression of the disorder makes the clinical diagnosis very difficult. Dural ectasia has been classified as a major diagnostic criterion; however, its prevalence is not known. We aimed to identify the true prevalence of dural ectasia in Marfan's syndrome, and to investigate its relation to aortic pathology. METHODS: A magnetic-resonance-imaging (MRI) study of the thoracic aorta and of the lumbosacral spine was done in an inclusive series of 83 patients with Marfan's syndrome to assess the presence and degree of dural ectasia and aortic involvement; 12 patients were younger than 18 years. 100 individuals who underwent MRI of the lumbar spine for routine clinical indications represented the control group; none of them had any potential causes for dural ectasia. FINDINGS: Dural ectasia was identified in 76 (92%) patients and none of the control group. The severity of dural ectasia was related to age; the mean (SD) age of patients with mild dural ectasia was 26 years (14) whereas that of those with severe disease (meningocele) was 36 years (9) (p=0.038). 11 of 12 patients younger than 18 years had dural ectasia. No association was found between aortic dilatation and dural ectasia. INTERPRETATION: Dural ectasia is a highly characteristic sign of Marfan's syndrome, even at an early age.

Coronary and peripheral artery remodeling in patients undergoing PTCA: An intracoronary and transcutaneous ultrasound study.

The aim of this study was to assess the relationship between the plaque burden of nonstenotic coronary artery segments and the wall thickness of peripheral arteries using intracoronary and transcutaneous ultrasound imaging, respectively. Intracoronary ultrasound (CVIS, 3.5 Fr) was performed in 27 patients undergoing percutaneous transluminal coronary angioplasty. Carotid arteries were imaged by B-mode ultrasound with semiautomatic edge detection and radial arteries by high resolution A-mode echotracking (NIUS 2). Quantitative measurements included coronary artery intima-media cross-sectional area (IM(CSA)) and cross-sectional narrowing (CSN), as well as intima-media thickness (IMT) and lumen radius (r) of the common carotid and the radial arteries. Intima-media thickness was increased in coronary, carotid, and radial arteries. Coronary arteries had an IM(CSA) of 7.7 +/- 2.5 mm(2) and a CSN of 24% +/- 8%. Despite this moderate plaque burden, lumen area was preserved (12.3 +/- 4.2 mm(2)) because of compensatory enlargement of coronary arteries. Right and left carotid and right radial arteries had an IMT of 575 +/- 78 microm, 570 +/- 129 microm, and 328 +/- 61 microm, respectively. There was no correlation between coronary IM(CSA) and carotid IMT (r = 0.07) or radial IMT (r = 0.02), and there was no correlation between coronary CSN and carotid IMT/r (r = 0.12), or radial IMT/r (r = 0.25). In conclusion, in these patients with symptomatic ischemic disease no relationship between IMT of the coronary arteries and IMT of carotid or radial arteries was found. Although increasingly popular, IMT of peripheral arteries may be of limited value as surrogate marker for the severity of coronary artery disease. Cathet. Cardiovasc. Intervent. 48:12-17, 1999.

[Invasive diagnosis of coronary heart disease in patients over 75 years old]. / Invasive Abklärung der koronaren Herzkrankheit bei über 75-jährigen Patienten.

Between January 1, 1993, and August 31, 1995, 268 patients over 75 years underwent coronary angiography at the University Hospital of Bern. Their clinical reports were analyzed in order to determine whether invasive diagnosis of coronary artery disease (CAD) is justifiable also in the elderly considering risks and complications. The main indication for coronary angiography were symptoms of ischemic heart disease. Twenty-nine underwent the procedure for planned cardiac surgery, mostly valve replacement. In 79% of patients, coronary angiography revealed CAD. In the remaining 21% there were no significant coronary stenoses, but 82% of them had valvular heart disease. Only 4% had neither coronary nor valvular heart disease. Following coronary angiography 63% of patients had a therapeutical intervention: 24% coronary angioplasty (PTCA), 13% bypass-grafting, 17% valve replacement, 8% combined surgery (revascularization and valve-replacement), and 1% another intervention. Four percent had no cardiac disease, 1% died before a planned surgery. The remaining 32% were continued on medical therapy. As indicators of appropriateness and success of the invasive procedure the rates of complications and the duration of hospitalization were analyzed. The incidence of deaths, myocardial infarctions, cerebral complications, and arrhythmias was five to ten times higher for cardiac surgery than for PTCA or conservative treatment. Invasive diagnosis and therapy of CAD in patients over 75 years can nevertheless be reasonable and successful if the decision is taken carefully considering risk factors and concomitant disease.

A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) Multicenter Trial of Angioplasty for Shock-(S)MASH.

AIM: To test whether emergency revascularization improves survival in patients with acute myocardial infarction and shock. METHODS AND RESULTS: Patients with acute myocardial infarction and early shock were randomized either to undergo emergency angiography, followed immediately by revascularization when indicated, or to receive initial medical management. In five of the nine participating centres, patients with shock but not randomized were entered in a registry. Only 55 patients could be randomized. Of the 32 patients in the invasive group, 30 (94%) underwent early angiography, 27 (84%) PTCA, and one (4%) CABG. Twenty-two (69%) died within 30 days in the invasive group vs 18/23 (78%) in the medically managed group (ns, RR=0.88, 95% confidence interval 0.6-1.2). Among the registry patients, 24/51 were excluded from randomization solely because of patient or physician preference for the invasive approach: 23 (96%) of them underwent emergency angiography, 21 (88%) PTCA, and 12 (50%) died within 30 days. Among the remaining registry patients (n=27) only nine (33%) underwent early angiography, nine (33%) PTCA and 20 (74%) died. CONCLUSION: We failed to demonstrate that emergency PTCA significantly improves survival in patients with acute myocardial infarction and early cardiogenic shock. Because the study was stopped prematurely, due to an insufficient patient inclusion rate, a clinically meaningful benefit of early reperfusion may have been missed.

[Bj"ork-Shiley heart vales at the Bern University Hospital. Long-term follow-up of 12 to 23 years after mitral and aortic valve replacement in 503 patients]. / Björk-Shiley-Herzklappen im Universitätsspital Bern. Langzeit Follow-up 12 bis 23 Jahre nach Mitral- und Aortenklappenersatz bei 503 Patienten.

Long-term follow-up, cardial complications and factors influencing the survival time have been investigated retrospectively in 503 patients, who underwent 344 aortic and 191 mitral valve replacements with Björk-Shiley heart valve prosthesis between 1973 and 1984 at the University Hospital of Berne, Switzerland. Informations were assessed from the patient's files and a questionnaire to the family physician. The cumulative follow-up contains a total of 4,810 patient years or a median of 14 years per patient. The median survival time was 19 years, hardly less than the normal life expectancy. Of the 135 patients found alive in 1996 66% had no cardiac problems at all. Two cases of outlet strut fracture of the Björk-Shiley valve were reported during the follow-up time. Both patients had a mitral valve replacement in 1982 with a 31 mm Björk-Shiley valve because of mitral stenosis. The most common complication was a thromboembolic incident (1.6 in 100 patient years). Furthermore eight cases of valve thrombosis, 16 of endocarditis and 24 of myocardial infarction occurred in this population. The study showed that survival time after heart valve replacement with Björk-Shiley valve is long. The mortality was elevated significantly with the following preoperative findings: severe dyspnea (x 2.0), pulmonary congestion (x 1.7) and increased cardiac size (x 1.5). The survival time was shorter when a valve prosthesis with a diameter larger than 27 was used or when in addition coronary heart disease, hypertension, diabetes mellitus or obesity were present.

M-cadherin and its sisters in development of striated muscle.

Cadherins are calcium-dependent, transmembrane intercellular adhesion proteins with morphoregulatory functions in the development and maintenance of tissues. In the development of striated muscle, the expression and function of mainly M-, N-, and R-cadherin has been studied so far. While these three cadherins are expressed in skeletal muscle cells, of these only N-cadherin is expressed in cardiac muscle. In this review, M-, N-, and R-cadherin are discussed as important players in the terminal differentiation and possibly also in the commitment of skeletal muscle cells. Furthermore, reports are described which evaluate the essential role of N-cadherin in the formation of heart tissue.