Syncope--an unusual presentation of ventricle dysfunction in a patient with Fontan circulation

We report a case of recurrent syncope in association with moderate ventricular dysfunction and mild AV-valve regurgitation in an 18-year-old girl, 4 years after she underwent total cavopulmonary connection surgery. Cardiac catheterization revealed a transpulmonary gradient of 1-2 mmHg. During exercise, a dramatic fall in blood pressure and blood oxygenation was observed, paralleled by an increase in heart rate and central venous pressure. Although a slight increase in pulmonary vascular resistance could not be excluded, the reaction was interpreted in terms of an extremely low transpulmonary gradient in association with ventricular dysfunction. Five months after heart transplantation, the patient has been completely free from syncope. Fontan circulation usually involves a delicate haemodynamic situation which may necessitate haemodynamic re-evaluations, including dynamic measurements of the central venous pressure during exercise. Also a moderate ventricular dysfunction may result in compromised pulmonary circulation which in turn may lead to syncope during exercise as a result of insufficient systemic circulation.     

Left ventricular diastolic filling is related to the atrioventricular plane displacement in patients with coronary artery disease

OBJECTIVE: Left atrioventricular plane displacement (AVPD) is often decreased and abnormalities in left ventricular diastolic filling are common in patients with coronary artery disease (CAD). This study was designed to assess the relationship between AVPD and diastolic filling in patients with CAD. DESIGN: AVPD was assessed by echocardiography and diastolic filling by transmitral and pulmonary venous pulsed Doppler in 170 consecutive patients (66 +/- 11 years) with proven CAD at coronary angiography. Diastolic filling was grouped as normal, mildly impaired and moderately to severely impaired. RESULTS: A simple linear regression analysis showed that AVPD decreased in relation to increased severity of diastolic filling impairment (r = -0.36, p < 0.0001). In a multiple regression analysis, ejection fraction, diastolic filling, age and body surface were independently correlated with AVPD. Each millimetre of decrease in AVPD increased the probability of impaired diastolic filling by 28%. CONCLUSION: AVPD was independently correlated with both left ventricular systolic function and diastolic filling in patients with CAD. Thus, given the same degree of ejection fraction, it was found that the greater the impairment in diastolic filling, the lower the AVPD.     

Typing for the human lewis blood group system by quantitative fluorescence-activated flow cytometry: large differences in antigen presentation on erythrocytes between A(1), A(2), B, O phenotypes

BACKGROUND: Lewis phenotyping by hemagglutination is an unreliable routine method for Lewis antigen designation. Now genomic typing of the Lewis gene is available. Additionally, flow cytometry has been used for typing. We wanted to compare the results of Lewis typing in healthy individuals using the three methods. MATERIALS AND METHODS: Ninety-three randomly selected plasma donors were genotyped for inactivating Secretor (FUT2) G428A and Lewis (FUT3) T59G, T202C, C314T, G508A and T1067A point mutations. All Le(a+b-) individuals (nonsecretors) were homozygous for the FUT2 G428A mutation and all Le(a-b-) individuals had inactivating mutations on both FUT3 alleles. Fixed erythrocytes were analyzed by fluorescence-activated flow cytometry and the results were compared with hem- agglutination and genotypic data. Antigen availability was expressed as median fluorescence intensity and as percentage positive cells with fluorescence intensities > or =10(2). RESULTS: Using an anti-Le(a) reagent a mean of 99% of erythrocytes from Le(a+b-) individuals and 1% of erythrocytes from Le(a-b-) or Le(a-b+) individuals were stained positive. Using an anti-Le(b) reagent, a mean of 71% of erythrocytes from A(1), 95% from B and 99% from O and A(2) Le(a-b+) individuals and less than 10% of erythrocytes from Le(a-b-) or Le(a+b-) individuals were stained positive. After papain treatment 100% of the erythrocytes from A(1) and A(1)B Le(a-b+) individuals stained positive without increase in background staining. The flow cytometric technique revealed large differences in staining intensities, within each ABO Le(a-b+) subgroup which was not directly correlated to plasma donation frequencies nor to Secretor or Lewis genotypes. CONCLUSION: Flow cytometry may prove valuable as a Lewis blood group typing technique but also as a research tool when investigating Lewis phenotypes of human erythrocytes.     

Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes

Objective: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. Background: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. Material and methods: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. Results: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l × min vs 2.6 mmol/l × min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l × min vs 54 pmol/l × min) and 30 min (2286 pmol/l × min vs 1198 pmol/l × min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (−1 min), proinsulin/insulin ratios (RPI) were lowest at 10–30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l × min vs 550 pmol/l × min) and a lower RPI at 30 min (6.0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. Conclusion: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese. Received: 15 June 1999 / Accepted in revised form: 9 August 1999     

Radiation-induced DNA Damage and Chromatin Structure

DNA lesions induced by ionizing radiation in cells are clustered and not randomly distributed. For low linear energy transfer (LET) radiation this clustering occurs mainly on the small scales of DNA molecules and nucleosomes. For example, experimental evidence suggests that both strands of DNA on the nucleosomal surface can be damaged in single events and that this damage occurs with a 10-bp modulation because of protection by histones. For high LET radiation, clustering also occurs on a larger scale and depends on chromatin organization. A particularly significant clustering occurs when an ionizing particle traverses the 30 nm chromatin fiber with generation of heavily damaged DNA regions with an average size of about 2 kbp. On an even larger scale, high LET radiation can produce several DNA double-strand breaks in closer proximity than expected from randomness. It is suggested that this increases the probability of misrejoining of DNA ends and generation of lethal chromosome aberrations.     

Pulmonary venous blood flow pattern in patients with univentricular hearts following total cavo-pulmonary connection

The objective of the study was evaluation of the pulmonary venous blood flow (PVF) pattern and the influence of ventricular function and atrioventricular valve regurgitation on this flow in patients with univentricular hearts post total cavo-pulmonary connection (TCPC). Transthoracic or transoesophageal echocardiographic studies were performed in 24 children with normal hearts (group A) and in 24 patients with univentricular hearts (group B). Ventricular function and atrioventricular valve regurgitation was semiquantitatively assessed. Systolic/diastolic maximal velocities and velocity time integrals (VTI) were measured from PVF tracings. Ejection fraction was measured by radionuclide angiography in 11 patients. Twelve patients underwent heart catheterization and angiography. In group B the PVF showed a biphasic flow velocity curve. The systolic integrals were smaller and the diastolic integrals were larger than in group A (6·4 vs. 13·0 cm, P = 0·0001, and 13·9 vs. 10·0 cm, P = 0·005). The pulmonary venous systolic flow fraction in 13 patients with an open fenestration and/or atrioventricular valve regurgitation grade 2–3 was significantly lower than in those 11 patients without fenestration and none/small regurgitation (0·19 vs. 0·40, P = 0·05). In conclusion, the PVF pattern in children with univentricular hearts palliated with TCPC is similar to the PVF pattern found in individuals with biventricular hearts showing a biphasic flow velocity curve despite the absence of pulsative pulmonary artery flow. The PVF in patients with TCPC-palliated univentricular hearts is influenced by atrioventricular valve regurgitation and fenestration flow.     

The platelet-specific alloantigen PlA1 (HPA-1a): a comparison of flow cytometric immunophenotyping and genotyping using polymerase chain reaction and restriction fragment length polymorphism in a Swedish blood donor population

BACKGROUND: There is an increasing interest in the development of rapid and reliable techniques for platelet alloantigen typing. STUDY DESIGN AND METHODS: By use of standardized flow cytometry and a specific human alloantiserum, 236 Swedish blood donors were immunophenotyped for the platelet-specific alloantigen, PlA1 (HPA-1a). RESULTS: Ten individuals (4.2%) had low fluorescence intensities and were considered PlA1- negative (HPA-1a-negative); all of them also demonstrated a PlA2/PlA2 (HPA-1b/1b) genotype in a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay of the underlying DNA polymorphism. The remaining population had clear positive fluorescence and was regarded as PlA1-positive (HPA-1a-positive). The fluorescence distribution histogram among PlA1-positive (HPA-1a-positive) individuals was dome-shaped, and those individuals who were homozygous for PlA1 (HPA-1a) could not be distinguished from those who were heterozygous. This finding was further substantiated by PCR-RFLP analysis of the PlA1/PlA2 (HPA-1a/1b) genotype; a heterozygous genotype was found among those having a medium fluorescence intensity as well as among those having a strong fluorescence intensity. CONCLUSION: Flow cytometry is a valuable tool for large-scale detection of PlA1 (HPA- 1a). However, flow cytometry based on only one antiserum cannot distinguish between homozygous and heterozygous carriers of PlA1 (HPA- 1a). For zygosity testing and when platelets are difficult to obtain, the PCR-RFLP technique is the assay of choice.     

HLA-B27 as a diagnostic screening tool in chronic low back pain

Forty-five of 52 consecutive patients with chronic low back pain were screened for presence of HLA-B27 antigen one year after they were included in a rehabilitative program. Six (13.3%) were positive and, when re-examined radiographically, 2 had signs of ankylosing spondylitis. The proportion of antigen-positive individuals is similar to that found in a population study of healthy Swedish blood donors, and within the range of other populations of healthy controls. It is concluded that HLA-B27 is of limited diagnostic value as a screening test for ankylosing spondylitis in a patient group with chronic low back pain.     

Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic.     

Early Psychological Preventive Intervention For Workplace Violence: A Randomized Controlled Explorative and Comparative Study Between EMDR-Recent Event and Critical Incident Stress Debriefing

This randomized controlled trial study aims to investigate the efficacy of an early psychological intervention called EMDR-RE compared to Critical Incident Stress Debriefing on 60 victims of workplace violence, which were divided into three groups: ‘EMDR-RE’ (n = 19), ‘CISD’ (n = 23), and ‘delayed EMDR-RE’ (n = 18). EMDR-RE and CISD took place 48 hours after the event, whilst third intervention was delayed by an additional 48 hours. Results showed that after 3 months PCLS and SUDS scores were significantly lower with EMDR-RE and delayed EMDR-RE compared to CISD. After 48 hours and 3 months, none of the EMDR-RE-treated victims showed PTSD symptoms.