Disease-related differences in antibody patterns against EBV-encoded nuclear antigens EBNA 1, EBNA 2 and EBNA 6.

Antibodies to Epstein-Barr virus (EBV) nuclear antigen family (EBNA) and three of its individual members, EBNA 1, EBNA 2 (A and B) and EBNA 6, were measured by anticomplement immunofluorescence (ACIF) in sera of 75 healthy controls, 13 patients with chronic EBV infection, 38 with non-Hodgkin lymphoma (NHL), 23 with Hodgkin's disease (HD), 105 with nasopharyngeal carcinoma (NPC) and 7 patients with infectious mononucleosis (IM). Their anti-EBV lytic antigens were also measured. We observed that: (1) anti-EBNA 2A and E6 rose in parallel 4-6 weeks after IM, followed by anti-EBNA 1 at 3-6 months, (2) all seropositive individuals had anti-EBNA 1; 74% also had anti-EBNA 2A and E6, (3) anti-EBNA 1 accounted for most of the anti-EBNA reactivity in non-IM sera. Striking disease-associated differences were noted on the humoral responses to the lytic and transformation-associated antigens. Compared to the controls, anti-EBNA 1, -EBNA 2A and -EBNA 6 were simultaneously four to 10 times higher in chronic reactivations, whereas only anti-EBNA 1 was elevated (10 times) in NPC. Individual EBNA titres were normal in NHL or HD patients.

Bone marrow transplantation in non-malignant disorders.

From January 1992 to December 1997, 21 consecutive patients (14 SAA, 3 SCID, 1 Fanconi anemia, 1 Diamond-Blackfan anemia, 1 mucolipidosis and 1 mucopolysaccharidosis type I.) were transplanted (16 HLA-id. family, 2 MUD and 3 haploidentical family donors) in a single center. The median follow up period is 41 months (range 7-76). The probability of 3.5 year overall disease free survival is 14/21 (67%), the transplant related mortality is 4/21 (19%). All the SCID patients are alive and disease free. 3 SAA patients had signs of fungal infection prior to transplant. They died in spite of intensive antifungal treatment resulting reduced DFS for SAA to 71%. Two patients with lysosomal storage disorders (mucolipidosis and MPS I.) rejected the haploidentical T-cell depleted graft 1 and 11 months after transplant, respectively. In 2 cases non-engraftment occured, both patients were retransplanted successfully.

Teratologic evaluation of 178 infants born to mothers who attempted suicide by drugs during pregnancy.

OBJECTIVE: To identify the teratogenic risk of large doses of various drugs taken by women in attempting suicide. METHODS: This population-based, prospective, epidemiologic study involved 559 women with pregnancy verified by a serum pregnancy test who were admitted to the toxicologic inpatient clinic in Budapest responsible for providing health services to chemically poisoned individuals from a population of 3 million. Each self-poisoned woman was matched for age and gestational age with a control selected from among participants in periconceptional care. RESULTS: Two of 559 self-poisoned pregnant women died. One hundred seventy-eight infants born to mothers who poisoned themselves during pregnancy either were examined personally or had appropriate medical data available. After excluding eight infants with fetal alcohol syndrome born to heavy-drinking mothers, the rate of congenital abnormalities in study infants (9.0%) did not significantly exceed the rate of control infants (6.1%). Thus, no teratogenic effect of drugs used for self-poisoning could be identified, even though large doses of drugs were used in 27 cases between the 3rd and 8th weeks of fetal development. This sample was not large enough to evaluate single drugs separately. CONCLUSION: Drugs taken by women in attempting suicide do not seem to pose a risk for structural birth defects in the offspring.

Birth weight and congenital anomalies following poisonous mushroom intoxication during pregnancy.

A series of 22 women who suffered from mushroom poisoning while pregnant have been identified among adults receiving treatment between 1960 and 1993 in a specialist clinic in Budapest, Hungary. In most cases, the poisonings were attributed to Amanita phalloides, verna, and related species. Of these, 20 went to term, and data were collected on gestational age, birth weight, and both major and minor congenital anomalies. Mean birth weight (but not gestational age) was lower than in the control series, suggesting that maternal poisoning may have led to intrauterine growth retardation. Two children were identified with major abnormalities (one of whom had fetal alcohol syndrome related to alcohol abuse by the mother). The prevalences of both major and minor anomalies were similar to the prevalence in the matched control group and to the rate in a more recent control series examined according to the same protocols. However, the statistical power to detect teratogenic effects is limited, especially as only five of the mothers suffered the poisoning episode during the first trimester.

Congenital abnormalities and indicators of germinal mutations in the vicinity of an acrylonitrile producing factory.

The results of an environmental mutation and teratologic epidemiological study are presented which was performed in inhabitants living in the surrounding region of an acrylonitrile factory in Nyergesújfalu. The endpoint of the study was congenital abnormalities in 46,326 infants born to mothers living in the 30 settlements of the study region within a 25 km radius of the acrylonitrile factory between 1980 and 1996. The ascertainment of cases with congenital abnormalities was based on the dataset of the Hungarian Congenital Abnormality Registry complemented with the review of pediatric, pathology and cytogenetic records. A particular attention was paid to the indicators of germinal mutations as sentinel anomalies, Down syndrome and unidentified multiple congenital abnormalities and the indicators of teratogens as the specific pattern of multiple congenital abnormalities. Three congenital abnormalities: pectus excavatum in Tata, 1990-1992 (OR with 95%CI: 78.5, 8.4-729.6), undescended testis in Nyergesújfalu between 1980 and 1983 (8.6, 1.4-54.3) and in Esztergom, 1981-1982 (4. 2, 1.3-13.5) and clubfoot in Tata, 1980-1981 (5.5, 1.5-20.3) showed significant time-space clusters in the study region. There was a decrease in risk of undescended testis with increasing distance from the acrylonitrile factory. An unusual increase was found in the combination of oral cleft and cardiac septal defects in multimalformed babies in Tatabánya, 1990. The detailed analysis of congenital abnormalities in all settlements of a given territory may help to detect clusters of congenital abnormalities and their possible relation to the environmental hazards.

Timing of suicide attempts by self-poisoning during pregnancy and pregnancy outcomes.

OBJECTIVE: The purpose of this study was to examine the timing and consequences of suicide attempts by self-poisoning during pregnancy. METHODS: A population-based prospective study was organised in the toxicological in-patient hospital in Budapest which is responsible for health services for adult inhabitants poisoned by ingesting chemicals in Budapest and the surrounding area involving 3 million people between 1985 and 1993. All women aged between 16 and 50 years (22969) who were admitted to the study hospital due to suicide attempts by drug ingestion were examined by a sensitive serum pregnancy test. RESULTS: Of 559 self-poisoned pregnant women, two died. The peak period of suicide attempts was found to be in the first postconceptual month and its majority resulted in a very early fetal loss. The second highest figure was recorded in the second postconceptual month. Thus, 61% of suicide attempts occurred before the third postconceptual month. Later pregnancies had a significantly lower proportion of attempting suicide parallel with advanced fetal development. CONCLUSIONS: Most suicide attempts by self-poisoning occurred after the early recognition of unwanted pregnancies and most resulted in a very early fetal loss. Pregnancies with advanced gestation months had a significantly lower proportion of attempting suicide.

An assessment of simple referee methods for the prediction of lean in pig carcasses.

A study was carried out in which carcass characteristics of 36 gilts were evaluated: 18 originated from the Hungarian 'Hungahyb' cross-breed, another 18, with undefined genetic background, from small private household plots. Two, rather simple substitute reference methods, called referee methods, were evaluated: measurement of carcass weight without skin and subcutaneous fat ('meat + bone'), and measurement of carcass weight without skin, subcutaneous fat and bone ('boneless meat'). Both methods gave a rather close relationship with the Kulmbach reference lean; however, removal of bone had presumably a beneficial effect on stability of prediction. The importance of preliminary information in quantitative form, giving a theoretical background for prediction equations, was presented as an example. Simple material balances could be formulated between reference lean and 'meat + bone' or 'boneless meat' content. Such material balances could not be set up with the indirect, rapid surrogate methods using mainly linear measurements (e.g. fat and muscle thickness, etc.) For this reason, as several other publications demonstrated, these latter methods seem to be more susceptible to bias than the referee methods. By determining the lipid content of the homogenised 'boneless meat' component, a 'lean' value adjusted to 3% fat content could be calculated from data which was compared to the dissected reference lean standardised also to contain 3% fat. These relationships, for several reasons discussed in this paper, were not as close as expected. So, further studies are needed to reveal these discrepancies.

[Prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) in the Hungarian population]. / A metiléntetrahidrofolát-reduktáz (MTHFR) gén polimorfizmusának (C677T) magyarországi gyakorisága.

MTHFR encodes a critical enzyme in folate and homocysteine metabolism and the C677T allele of the MTHFR gene has some association with an increased risk for neural-tube defects and for adult cardiovascular diseases. As part of an international collaborative study the prevalence of C677T homozygous genotype was 11.1% while the frequency of C677T heterozygous condition was 45.2% in the Hungarian neonate sample. These findings underscore the clinical importance of the C677T variant in the Hungarian population and urge population-based prevention of conditions related to such gene.

[Cases of diseases registered with the Genetic Counseling Service during the past 20 years, in the light of their etiology]. / Genetikai Tanácsadónk eseteinek alakulása a kóreredet tükrében az elmúlt 20 évben.

The authors analyse the experiences of their Genetic Counseling Clinic between 1979-1992. They show the formation of the motives of presenting and consulting. They range the consultants in three etiological categories (genetical, teratological and clinical entities). The proportion of new consultants increased fourfold and this tendency documents unambiguously the claim of family planners for this very important medical service. The proportion of Mendelian disorders, mutagen risk and consanguinity are relatively continuous. Because of teratogen risk the rate of presenting decreased moderately. The proportion of consultants shows a definite increase of multifactorial frequent disorders, which they value as a favorable tendency. For decreasing of unjustified cases they suggest the necessity of pre-screening.

[Prophylactic and therapeutic use of immunoglobulins in patients with bone marrow transplantation]. / Immunglobulinok profilaktikus és terápiás alkalmazása csontvelötranszplantált betegekben.

Eleven children were transplanted in our BMT Unit. All but one received standard IVIG preparations in doses of 100 mg/kg b. w. regularly on days before and after transplantation -1, +14, +28, +60 and +90, respectively, and anti-CMV hyperimmune globulin (Cytotect) was given to six patients in the same doses, respectively. In spite of the severe immunodeficiency bacterial infections were verified only in four patients, and CMV infection in three. New infection only occurred in two of the three patients, who hadn't been given CMV prophylaxis, while in the group of six children having been given Cytotect prophylaxis only one became infected from endogenous reactivation of CMV. Therapeutic application of immunoglobulin compounds were used in four of our transplanted patients. Two of them suffered from sepsis during transplantation, one from protracted immunoneutropenia and one from CMV antigenaemia after the transplantation, respectively. Our conclusion is that the administration of immunoglobulins may contribute to the prevention of infections and to the treatment of some complications in BMT recipients. Anti-CMV immune globulin seems to be more effective than standard IVIG in the prevention of CMV infection.

[Timing of attempted suicide by drug poisoning during pregnancy and pregnancy outcome]. / A terhesség alatti gyógyszeres öngyilkosságok idöpontja és a terhességek kimenetele.

Suicide attempts by drug ingestion during pregnancy provides an opportunity to study the teratogenicity of large doses of drugs in human beings. Data of a population-based prospective study of all pregnant women admitted to the toxicological inpatient hospital in Budapest which is responsible for the health provision of chemical poisoned persons from a 3 million study population. Of 22,969 self-poisoned women, 645 were pregnant and 559 attempted suicide by drug ingestion during pregnancy during the study period (1985-1993). Two died. The peak of suicide attempts was found in the first month of fetal development, and its great majority resulted in a very early fetal death, the so-called chemical pregnancy. Thus 61% of suicide attempts occurred before the third month. Later pregnancies had a protective effect against suicide parallel with advanced months of fetal development.

[The importance of molecular genetic diagnosis of Martin-Bell disease in genetic counseling]. / A Martin-Bell-kór molekuláris genetikai kórismézésének jelentösége a genetikai tanácsadásban.

The female consultant had two mentally retarded boys from her two marriages. The clinical symptoms and Fra-X chromosomes indicated their Martin-Bell disease. The daughter of the consultant is healthy and Fra-X negative. She is pregnant and insisted on her molecular genetic diagnosis due to an international collaboration. Both affected brothers had FRAXA genes with a full mutation including more than 200 CGG methylated repeats. The consultant female was in the phase of premutation, however, her healthy daughter had two normal 50% methylated genes with 19 and 26 CGG repeats. Thus there is no recurrence risk for Martin-Bell disease in her fetus.

[Leukocyte adhesion defect--a rare form of congenital immune deficiency]. / Leukocita adhéziós defektus (LAD)--a veleszületett immundefektusok ritka formája.

Leukocyte adhesion defect (LAD) is an inherited defect of phagocytic function. This disorder is characterised by delayed separation of the umbilical cord, severe recurrent bacterial infections, impaired formation of pus, and high leukocyte counts. The granulocytes have severe defect in their chemotactic mobility and endocytosis. The disease is attributed to the absence of the leukocyte adhesion molecules. (CD11/CD18), which can be verified with monoclonal antibodies. The authors describe the disease-process of the first patient diagnosed in Hungary. Perinatally the omphalitis, periumbilical abscess and periproctal abscess leading to rectovaginal fistula, in the first months the otitis, mastoiditis, and expressed leukocytosis referred to the impaired function of phagocytic cells, which was verified by laboratory tests as well. The decreased inflammation and cicatrization were also striking. This severe form of LAD can be cured only by bone marrow transplantation with preliminary sanitation of the foci of infection. It took about six months. Unfortunately, the patient died of sepsis immediately before transplantation.

[The bone-marrow transplantation program in Hungary: report from the period 1990-1995]. / Csontveló-transzplantációs program Magyarországon: beszámoló az 1990-1995 közötti idószakról.

The article summarises the statistical data of bone marrow transplantation (BMT) carried out in Hungary between 1990-1995 in yearly distribution. Since the first BMT up to the end of 1995, 168 BMT were performed. The number of transplantations since 1990 to our days was gradually increasing. As a result of this activity in the three transplantation centers (National Institute of Haematology and Immunology, St. László Hospital and County Hospital in Miskolc) 36 allogeneic and 12 autologous BMT were performed in 1995. Out of the allogeneic BMT cases, 14% of them were completed with unrelated, donors in the last three years. The most frequent indications for allogenic BMT are: chronic myeloid leukaemia (CML), acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), myelodysplasia, severe aplastic anaemia. Child allogenic BMTs are carried out on pediatric patients in St. László Hospital in leukaemia, severe aplastic anaemia cases and children born with immunodeficiency. Autologous BMTs started in an organised way in 1995 for adult patients in cases of non-Hodgkin lymphoma, Hodgkin lymphoma and for children with solid tumour indication in the Miskolc Centre. BMT activity in Hungary compared with international data, especially within Europe, shows a significant drop behind. To calculate for ten million inhabitants, the optimal BMT activity should be between 100-200 transplantations (allogeneic and autologous BMT together) in 1994. Among the Central European countries Hungary and Poland fall most behind. Autologous BMTs in most countries of Europe are above of allogeneic BMTs in numbers as indication in cases of lymphoma and solid tumours (first of all mamma carcinoma) comes into focus. This summary emphasises the most important difficulties in connection with the development of the National BMT program.