[Clinical research at the European LeukemiaNet].
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Publications and source records attributed to K Adam.
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The aim of our study was to investigate the genetic linkage between mite allergic bronchial asthma and HLA class I and II antigens and haplotypes. Sixty Greek children with allergic bronchial asthma due to mite sensitivity (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and their family members were typed for HLA class I and II antigens (total 263 subjects). One hundred and twenty-five healthy, unrelated Greek children without medical history of atopy were also typed as control group. Major histocompatibility complex class I and II gene analysis revealed that only HLA-DRB1*04 and HLA-DQA1*0301 alleles are possibly important factors in the development of atopic asthma in Greek children with sensitivity to mites. No significant differences among the HLA-DRB1*04 subtypes have been established. Transmission disequilibrium test revealed that no specific HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles were transmitted preferentially to the affected children. HLA-DQB1*0301-4 alleles were associated with high levels of total serum immunoglobulin E in affected children. The study of the HLA haplotypes failed to demonstrate any significant association between any extended or natural selection haplotype and mite allergic bronchial asthma in Greek children.
OBJECTIVE: The aim of this study was to investigate the relationship between HLA molecules and the positive or negative response of atopic patients to specific immunotherapy (SIT). METHODS: We studied 42 atopic multisensitive patients undergoing grass pollen immunotherapy, 42 parents of patients (30 mothers and 12 fathers) and 173 control individuals. HLA class I and class II antigens were typed by a microlymphocytotoxicity test. The typing of DRB1* alleles for atopic patients and their parents was based on the reverse hybridization principle, while for the control group, DNA-RFLP and PCR-SSP methods were used. RESULTS: The frequency of B14 and DRB1*1101-4 antigens/alleles, as well as the A2B5DR11 haplotype, showed a statistically significant difference in those patients who responded to immunotherapy. On the other hand, HLA-A28, B8 and DRB1*0301 antigens/alleles, as well as the frequency of the A1B8 and A1B8DR3 haplotypes, were found to be significantly higher in patients who responded poorly to SIT. DISCUSSION: Our findings support the hypothesis that treatment responsiveness may show an association to HLA molecules, which could thus play a role in the immunological selection and monitoring of atopic patient candidacy for SIT.
OBJECTIVE: To examine the association of unresolved and unclassifiable attachment with dissociative symptomatology in a sample of 133 adolescents in psychiatric treatment. METHOD: The study compared 69 adolescents who were unresolved and unclassifiable with 64 adolescents who were not unresolved and unclassifiable. Attachment organization was assessed using the Adult Attachment Interview (AAI). Dissociative symptomatology was assessed using a scale derived from the Youth Self Report (YSR) behaviour checklist. RESULTS: A continuing unresolved and unclassifiable response to attachment-related trauma was correlated with dissociative symptomatology for both male and female adolescents. CONCLUSIONS: Cognitive disorganization may be an important variable mediating between the effects of earlier traumatic caregiving experiences and later dissociative symptoms.
This article reports on the Adolescent Unresolved Attachment Questionnaire (AUAQ), a brief questionnaire that assesses the caregiving experiences of unresolved adolescents (as recipients of caregiving). The AUAQ was developed and validated in a large normative sample (n = 691) and a sample of 133 adolescents in psychiatric treatment. It is a self-report questionnaire consisting of 3 scales with Likert-type responses ranging from strongly disagree to strongly agree. The Aloneness/Failed Protection Scale assesses the adolescent's perception of the care provided by the attachment figure. The Fear Scale taps the fear generated by the adolescent's appraisal of failed attachment figure care. The Anger/Dysregulation Scale assesses negative affective responses to the perceived lack of care from the attachment figure. All scales demonstrated satisfactory internal reliability and agreement between scores for adolescents (n = 91) from the normative sample who completed the AUAQ twice. Adolescents in the clinical sample also completed the Adult Attachment Interview (AAI; C. George, N. Kaplan, & M. Main, 1984/1985/1996); the AUAQ demonstrated high convergent validity with the AAI.
BACKGROUND: Paternal dispermy can be the pathogenesis of complete molar pregnancy. CASE: A 23-year-old, white woman, gravida 4, para 1, was pregnant with a twin gestation by ovulation induction with metrodin. Ultrasound evaluation confirmed an intrauterine pregnancy in conjunction with what appeared to be a hydatidiform mole. The karyotype in the molar pregnancy, obtained from chorionic villus sampling, showed a pair of paternally derived inverted chromosomes 9, confirming the diagnosis of a complete mole. Uncontrollable hemorrhage with a rapid rise in the beta-human chorionic gonadotropin titer necessitated evacuation of the uterus. The patient was followed with beta-human chorionic gonadotropin titers for a year, with no evidence of recurrence. CONCLUSION: This case illustrates paternal disomy in a complete molar pregnancy documented by a paternal chromosome 9 inversion.
BACKGROUND: Little information is available about changes in left ventricular diastolic function during pregnancy. We used mitral inflow and pulmonary venous flow profiles to evaluate left ventricular diastolic function in 37 healthy pregnant women 26 to 41 years old (mean, 32 years). METHODS AND RESULTS: Echocardiographic studies were performed at the end of each trimester. Eight subjects (control group) underwent similar testing 1 to 3.5 months (mean, 1.7 months) postpartum. During pregnancy, the cardiac output increased significantly as a result of an increased heart rate and, to a lesser degree, stroke volume. Significantly decreased systemic vascular resistance and increased left ventricular mass were also noted. Peak mitral flow velocity in early diastole (E) increased 13. 3% during the first trimester and remained at the high end of normal throughout pregnancy. Peak A-wave velocity (A) increased maximally in the third trimester. Compared with control subjects, first-trimester subjects had a significantly increased E/A ratio. The ratio subsequently decreased, reflecting the augmented A-wave velocity. Pulmonary venous peak systolic forward flow velocity increased, peaking in the second trimester (nonsignificant), but returned to baseline levels postpartum. The pulmonary venous diastolic time-velocity integral decreased significantly from the first to the third trimester. Peak pulmonary venous reverse flow velocity at atrial contraction increased significantly, without being markedly changed in duration. CONCLUSIONS: Pregnancy, a chronic, natural volume-overload state, has important effects on hemodynamic and echocardiographic variables. Based on pulmonary venous flow and left ventricular inflow velocities, our results provide a standard reference concerning diastolic filling dynamics by trimester.
Aortic stenosis in pregnancy can be a life-threatening condition, but fortunately it is rare. In the modern era, careful obstetric and cardiologic monitoring, particularly through echocardiography, have improved fetal and maternal outcomes. However, a test that could predict outcome has not been available for patients with aortic stenosis who seek prepregnancy counseling. We report a case in which exercise Doppler echocardiography was used to predict cardiac function and maximal gradients in a woman with a bicuspid aortic valve who wished to become pregnant.
The aim of this study was to investigate the association of different groups and subgroups of juvenile chronic arthritis (JCA) with HLA class II (DR, DP, DQ) alleles and/or haplotypes. Groups and subgroups were mainly distinguished on the basis of the type of onset, the course and complications of the disease, and some predefined disease markers according to the criteria proposed by the ILAR Standing Committee (Chile, 1994). On the basis of these criteria the following five JCA groups and their subgroups were included in the study: (1) define systemic onset (n = 25) and systemic progressing to persistent arthritis (n = 14); (2) JCA of oligoarthritis onset (O-JCA, n = 124) and of oligoarthritis onset and course (n = 98), O-JCA of early (< 6 years) or late (> 6 years) onset (EOO-JCA n = 71 and LOO-JCA n = 44), O-JCA with ANA positive (n = 69) or negative (n = 55) and O-JCA progressing to extended arthritis (n = 22); (3) JCA of polyarthritis onset (P-JCA) with rheumatic factor (RF) negative (n = 29), and P-JCA RF negative with antinuclear antibodies (ANA) positive (n = 13) or negative (n = 16); (4) JCA complicated with chronic anterior uveitis (CAU, n = 32); (5) juvenile psoriatic arthritis (n = 20). To assess the HLA allele frequencies in the above 223 Greek children with JCA, these frequencies were compared to those of 98 age-matched and 250 adult controls. The main findings were the following. A common HLA-DRB1* allele was not involved in the JCA groups and subgroups studied; on the other hand, the DQA1*0501 allele was found to be associated with different JCA groups/subgroups (O-JCA, P-JCA RF-negative ANA-positive, JCA with CAU), probably suggesting a closer relationship of this locus with the immunogenetic background of JCA. The DPB1*0201 allele was associated with the development of either EOO-JCA or CAU. Susceptibility to CAU was stronger when the DPB1*0201 was combined with the presence of DRB1*13. Another allele, DQB1*0301, was also associated with O-JCA and CAU. Finally, no specific HLA class II allele was found to be related to the presence of ANA or psoriatic lesions or to the severity of the arthritis. Our findings suggest that the wide clinical and laboratory spectrum of JCA is associated with an immunogenetic background that is linked with HLA alleles of more than one locus. Some of them, such as the DPB1*0201 allele, confer susceptibility to certain clinical onsets and courses or complications of the disease. The rapidly advancing techniques of typing of DNA profiles may lead to more definite conclusions.
BACKGROUND AND AIMS OF THE STUDY: An association between Graves' hyperthyroidism (G) and mitral valve prolapse (MVP) has been reported, but possible genetic linkage between the two disorders has not. METHODS: One hundred and five patients (pts) with G were studied after therapy, in a euthyroid state. MVP (auscultatory plus echocardiographic findings) was present in 33 pts (31%). Frequency of human lymphocyte antigens (HLA) in pts with G and in pts with G plus MVP was compared to 170 normal subjects (NL). There was no difference in HLA-A antigens among the three groups. RESULTS: The frequency of HLA B-15 was greater in pts with G plus MVP (18.9%) compared to NL (3%) and to G without MVP (4.2), p < 0.01. The frequency of HLA-B39 was greater in G without MVP (13.8%) compared to NL (4.1%), p < 0.01. The HLA DRB1*1601-2 was more frequent in G with (30.3%) or without (29.2%) MVP compared to NL (13.5%), p < 0.01. The frequency of HLA DRB1*1401-10 and DQA1*0104 were greater in NL (16.5%) compared to G with (3.0%) or without (4.2%) MVP, p < 0.01. CONCLUSIONS: The data confirmed previous observations that the frequency of MVP is high in pts with G. Further, the data indicated a possible genetic linkage between the two abnormalities.
One of the many causes of fetal hydrops is fetomaternal hemorrhage. This report presents a pregnancy with fetomaternal hemorrhage that was treated with serial combined intravascular and intraperitoneal fetal transfusions, resulting in a good outcome. A 26-year-old woman seen for ultrasonographic evaluation was found to have a fetus with hydrops fetalis. Fetal blood sampling demonstrated severe fetal anemia (hematocrit 16.4%). The initial Kleihauer-Betke test result on maternal blood was 6% fetal cells. The fetus was transfused five times over a 24-day period by means of a combined intravascular and intraperitoneal route. The fetus also received one platelet transfusion for thrombocytopenia. The pregnancy resulted in a good fetal outcome without the need for postpartum transfusion. This case represents successful treatment of fetal anemia and nonimmune hydrops with a serial combined intravascular and intraperitoneal transfusion technique.
OBJECTIVE: Our purpose was to determine the effects of orally administered nimodipine on selected maternal and fetal parameters in patients with preeclampsia. STUDY DESIGN: Ten consecutive patients were given 30 mg of nimodipine orally every 4 hours from admission until 24 hours after delivery. Maternal and fetal cerebral blood velocity, umbilical artery blood velocity, fetal heart rate variability, maternal blood pressure and heart rate, and transplacental passage of the drug were studied. All 10 patients were delivered within 24 hours of the first dose of nimodipine. RESULTS: There was an acute and significant reduction in the pulsatility index in the smaller diameter maternal cerebral arteries (ophthalmic and central retinal) and in the fetal middle cerebral artery. The umbilical artery systolic/diastolic ratio was also significantly reduced. Maternal blood pressure was controlled without the need for other antihypertensive medication, and although there was an increase in heart rate after administration of the drug, it was well tolerated. Nimodipine reached significant maternal and fetal levels within 2 hours. CONCLUSIONS: Nimodipine is rapidly absorbed after oral administration and has significant maternal and fetal cerebral vasodilator activity. It is an effective, easily administered antihypertensive agent when used in patients with preeclampsia.
The serological identification of HLA class II alleles is often doubtful. Since accurate HLA typing is essential for the matching of donor-recipient pairs in allogeneic transplantation, an effort was made to establish DNA restriction fragment length polymorphism (RFLP) typing and to assess the correlation between the serological and RFLP techniques in the population of Northern Greece. One hundred and two healthy individuals (204 HLA-DR alleles) from Northern Greece were HLA-DR, DQ typed with both the microcytotoxicity and the Taq I RFLP method, using three exon-specific probes. DNA-RFLP typing revealed (1) concordant results with serology in 69.9% (142/204) of the alleles and (2) at least one HLA-DR allele discrepant to serology in 30.4% (62/204) of the alleles. Incorrect serological DR types (weak reactions or inability to distinguish between two alleles with a common epitope) were identified in 54 alleles (26.5%), while 3.9% (8/204) of serological "blank" alleles turned out to be definable alleles by RFPL. Of the individuals tested, 10.8% (11/102) were DR-homozygous by RFLP. This comparison of results obtained by serology and RFLP demonstrated the necessity of the clinical application of DNA typing, especially for organ transplantation where accurate HLA typing has an important influence on graft survival.
The purpose of this study was to present the new computer program that we developed in the regional tissue typing laboratory (R.T.T.L.) and use for the selection of the most suitable recipient for cadaveric allografts in a more efficient way. This new program was written and compiled in TURBO PASCAL 6.0, sorts all possible recipients to the HLA type of a donor, checks for the existence of splits and utilises them, and when requested, gives out results to more specific inquiries, i.e. all compatible recipients from 2DR2B2A to 1DR0B0A matching. It can also forecast success percentages according to different factors, i.e. combination of donor's and recipient's ages, HLA matching etc. The material used for this study were the patients who are registered in the formal cadaveric transplantation list of R.T.T.L. We have used this program since 2 January 1992 together with the old one. Since then we found that the new program is faster in sorting all the possible recipients of cadaveric renal allografts according to the criteria already mentioned. The total selection time, with all the criteria activated, averages a few seconds, whereas with the old program it took approximately 2 min just for the sorting of HLA matching, without any other criteria activated. In the printout of the final result of each inquiry are all the possible recipients in the sorted order together with relevant data (telephone number, address etc.). As a result, the laboratory personnel has been free from the tedious task of this sorting which was initially done by hand and the possibility of error has been eliminated. The program was developed exclusively by doctors and all the updates needed are done by the users. More important, however, is the fact that in many cases the time of cold ischaemia was reduced by more than 30 min with all the obvious advantages for the longevity of the graft's life.
OBJECTIVE: To compare two different Doppler echocardiographic techniques for the assessment of the transmitral area in pregnant patients with native mitral valve stenosis or prosthetic mitral valves. METHODS: Eight consecutive gravid women with prosthetic mitral valves or obstructive native mitral valve disease were evaluated using both the pressure half-time and the continuity equation Doppler echocardiographic methods. Heart rate, cardiac output, and transmitral valve gradient and area were calculated. These studies were repeated postpartum in five women. Differences between the two methods were assessed by characterizing the absolute differences between the mean and standard deviation and by paired t tests. Linear regression analysis was also applied. RESULTS: For the five women who also had postpartum studies, antepartum data were similar to those of the full set of eight patients. Postpartum heart rate, cardiac output, and transvalvular gradient were lower than antepartum measurements. Calculations using the continuity equation yielded comparable antepartum and postpartum estimates of transmitral areas (1.31 +/- 0.41 versus 1.32 +/- 0.44 cm2, respectively, r = 0.96). These estimates were also consistent with the initial clinical presentation. In contrast, antepartum transmitral valve areas calculated using the pressure half-time technique (2.67 +/- 0.61 cm2) were markedly higher than postpartum (1.94 +/- 0.58 cm2). The correlation between the estimates of antepartum valve area given by the two methods was not statistically significant (r = 0.02). In contrast, there was excellent postpartum correlation of transmitral area between the methods (r = 0.99), despite a significant difference (P < .001) in the transmitral area calculated with each technique. CONCLUSIONS: The results indicate that Doppler echocardiographic estimates of the transvalvular area using the continuity equation technique during pregnancy are valid. In contrast, estimates of area using the pressure half-time technique in pregnant patients are dubious and could result in life-threatening consequences.
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We present the case of a 30-year-old woman, 33 weeks pregnant, whose pregnancy was complicated with the rare condition of pheochromocytoma-induced myocardial infarction. Alpha- and beta-adrenergic blockade was instituted immediately for control of hypertension and arrhythmias. Two weeks after myocardial infarction, fetal maturity was documented, and the patient underwent cesarean section delivery of a 6-lb, 6-oz baby girl. The delivery was followed immediately by excision of a 7- x 6- x 4.5-cm tumor, which was confirmed to be a pheochromocytoma by histologic examination. Her post-operative course was uneventful. Our case study and a review of the literature show that the key to successful fetal and maternal outcome is early diagnosis, which can be confirmed by 24-hour urine testing of catecholamine and metanephrine levels. If the tumor is diagnosed before 20 weeks' gestation, we recommend immediate surgical removal of the tumor and continuation of the pregnancy to term. The management of the patient who presents between 20 and 24 weeks' gestation will depend on the uterine size in terms of tumor access. After 24 weeks, the pregnancy should be carried to term, at which time delivery by cesarean section will be followed by tumor excision. Postoperative care should include appropriate cardiovascular investigation and ongoing serial measurements of urinary catecholamines.