["Kroly Than" Pharmacy, Sopron, Hungary]. / Than Károly gyógyszertár, Sopron.

The hundred year-long history of the "Károly Than" Pharmacy is surveyed. The widespread and versatile professional, humanitarian and public life activities from the turn of the century to the nationalisation and than to the privatisation are described. The paper also commemorates Professor Károly Nikolics, the prominent director and scientist, who has outstanding merits in making the city of Sopron one of the major headquarters of Hungarian pharmacy.

Acute effect of KA-672, a putative cognitive enhancer, on neurotransmitter receptor binding in mouse brain.

7-Methoxy-6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]-3,4-dim ethyl-2H-1-benzopyran-2-one hydro-chloride (KA-672), structurally related to naturally occurring coumarins, has been described as a potential drug for enhancing cognitive functions. However, a detailed characterization of the pharmacological profile of KA-672 in vivo is still lacking. Quantitative neurotransmitter receptor autoradiography was used as a tool to screen for KA-672-induced changes in a number of transmitter receptors including cholinergic, noradrenergic, glutamatergic, GABAergic, and serotonergic subtypes throughout the brain. Two hours following treatment of mice with 1 mg/kg KA-672 per os, slight increases of nicotinic and M1-muscarinic cholinergic receptor binding, of alpha2-and beta-adrenoceptor as well as 5-HT1A receptors in various cerebral cortical regions were observed, whereas 5-HT2A binding sites were strikingly increased throughout the brain following KA-672 treatment. In contrast, (+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding was significantly decreased in some cortical regions after drug treatment. No effects of KA-672 treatment on N-methyl-D-aspartate, kainate, GABA(A) and benzodiazepine receptor as well as M2-muscarinic cholinergic and high-affinity choline uptake binding were observed. As interactions between the cholinergic, noradrenergic and serotonergic neurotransmission have been stressed to play important roles in realizing learning and memory events, the cognition-enhancing effects of KA-672 may be due to this complex in vivo pharmacological profile of KA-672.

Ethical issues in umbilical cord blood banking. Working Group on Ethical Issues in Umbilical Cord Blood Banking.

OBJECTIVE: Banking umbilical cord blood (UCB) to be used as a source of stem cells for transplantation is associated with a set of ethical issues. An examination of these issues is needed to inform public policy and to raise the awareness of prospective parents, clinicians, and investigators. PARTICIPANTS: Individuals with expertise in anthropology, blood banking, bone marrow transplantation, ethics, law, obstetrics, pediatrics, and the social sciences were invited to join the Working Group on Ethical Issues in Umbilical Cord Blood Banking. EVIDENCE: Members were assigned topics to present to the Working Group. Following independent reviews, background materials were sent to the Working Group. CONSENSUS PROCESS: Individual presentations of topics at a 2-day meeting were followed by extensive group discussions in which consensus emerged. A writing committee then drafted a document that was circulated to the entire Working Group. After 3 rounds of comments over several months, all but 1 member of the Working Group agreed with the presentation of our conclusions. CONCLUSIONS: (1) Umbilical cord blood technology is promising although it has several investigational aspects; (2) during this investigational phase, secure linkage should be maintained of stored UCB to the identity of the donor; (3) UCB banking for autologous use is associated with even greater uncertainty than banking for allogeneic use; (4) marketing practices for UCB banking in the private sector need close attention; (5) more data are needed to ensure that recruitment for banking and use of UCB are equitable; and (6) the process of obtaining informed consent for collection of UCB should begin before labor and delivery.

Ethical aspects of banking placental blood for transplantation.

Transplantation of blood cells harvested from the umbilical cord immediately after birth has been effective in repopulating the bone marrow. These placental blood transplantations may be safer than conventional bone marrow transplantations and may suspend the need to harvest bone marrow, a process fraught with difficulties. Further understanding and advancement of this emerging technology require developing large banks of placental blood. In this article, we examine some of the ethical issues associated with placental blood banking, including (1) questions about ownership of the tissue, (2) the necessity and nature of obtaining informed consent from parents for harvesting placental blood and the information-gathering process associated with it, (3) obligations to notify parents and children of the results of medical testing for infectious diseases and genetic information, (4) matters of privacy and confidentiality related to such information, and (5) the need for fair and equitable harvesting of and access to placental blood.

A model for the assessment of students' physician-patient interaction skills on the surgical clerkship.

Physician-patient interaction skills are predominantly taught by successful role modeling but are rarely evaluated formally and systematically. This study describes a new model for the assessment of student physician-patient interaction skills and reports results of use in 78 third-year medical students on clerkships at two institutions. A single nurse instructor at each institution evaluated these skills using an 18-item checklist during student performance of wound care and dressing changes. Students were focused on the evaluation of their technical skills and were unaware of the evaluation of their interaction skills. Immediate feedback on performance was provided. The mean percentage score for the interaction skills was 35%, and no improvement was noted with greater clinical experience (later rotations). We conclude that there is a striking deficiency in physician-patient interaction skills among third-year students. The model described is effective for both evaluation and feedback.

Variable association of HLA-A2 in men with early-onset Alzheimer disease.

In the present study, we attempted to replicate the finding of an increased frequency of HLA-A2 in men with early-onset (less than or equal to 60 years) Alzheimer disease (AD). HLA data obtained on 167 patients (including 19 men with early-onset AD) from three geographic regions (North Carolina, Great Britain, and Finland) failed to replicate the result. A recent prospective study from Oregon, however, confirmed the association. Studies demonstrating the association suggest its presence in sporadic rather than familial AD. These results indicate a variable HLA/AD association, with some factor such as geographic region or disease familiality contributing to this variability.

Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency.

T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from T.D. T cells had normal Km, heat stability, and sensitivity to ADA inhibitors. Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+ T.D. T cells was shown by allele-specific oligonucleotide hybridization to possess the same mutations (Arg101----Trp, Arg211----His) previously found in the ADA-T.D. B cell line GM 2606 (Akeson, A. L., D. A. Wiginton, M. R. Dusing, J. C. States, and J. J. Hutton. 1988. J. Biol. Chem. 263:16291-16296). Our findings suggest that one of these mutant alleles can be expressed selectively in IL-2-dependent T cells as stable, active enzyme. Cultured T cells from other patients with the Arg211----His mutation did not express significant ADA activity, while some B cell lines from a patient with an Arg101----Gln mutation have been found to express normal ADA activity. We speculate that Arg101 may be at a site that determines degradation of ADA by a protease that is under negative control by IL-2 in T cells, and is variably expressed in B cells. Il-2 might increase ADA expression in T cells of patients who possess mutations of Arg101.

Tests of genetic markers on aborted fetal material.

Women who conceive as a result of rape often elect to abort the fetus. We describe twelve cases where genetic markers were tested on the aborted fetal material to provide evidence of the genetic constitution of the rapist. Two cases are presented in detail, and the problems encountered with the testing are discussed.

Alloantibody responses in multiply transfused sickle cell patients.

Fifty-six adult and 15 pediatric black patients with sickle cell disease were studied to determine their antibody responses to repeated transfusions of red cells. Red cell antibodies were determined retrospectively; anti-lymphocyte antibodies (class I and II) were determined on the single, most recently drawn blood sample. All adults were HLA-A, B, C, DR and DQ typed. Ten percent of the individuals with less than 50 transfusions, but greater than 50% with 100 transfusions or more, had red cell antibodies. The percentage of patients producing anti-red cell antibodies increased consistently with the number of transfusions (p = 0.0062). Women were more likely to become sensitized to red cell antigens than men (p = 0.008), and nulliparous women more likely than multiparous women. Children were also sensitized to red cell antigens (20%), and to a high degree to lymphocyte antigens (73%). No HLA association was found with increased propensity to red cell sensitization. A weak association of HLA DR5 and DR7 with failure to become sensitized to lymphocyte alloantigens was observed, but did not reach statistical significance. Our results suggest that, while genetic factors influencing transfusion response almost certainly exist, other factors such as number of transfusions, age, sex and parity need to be examined to provide accurate projections of risk in chronic transfusion.

The effect of differences in gene frequency on probability of paternity.

Knowledge of gene frequencies in populations is required for the calculation of probability of paternity. The question remains open as to the degree of accuracy of gene frequency estimates required to give accurate probability of paternity figures. This is of special concern in the HLA system, which has haplotype frequencies known to vary in populations. This paper presents computer simulation data comparing probability of paternity calculations using HLA data from California and North Carolina. Comparisons were made between geographic regions, and between blacks and whites within a geographic region. It was found that when the absolute probability of paternity is high, the average differences induced were small, but at lower probabilities the changes can be large. Differences were most pronounced between black and white populations. Examples of individual cases are given to illustrate the huge differences that can be induced in some cases by changing gene frequency.

Calcification of entheses associated with X-linked hypophosphatemic osteomalacia.

We undertook a retrospective analysis of 26 patients with X-linked hypophosphatemic osteomalacia (or rickets), whose ages ranged from 1 to 62 years and who were from 11 different kindreds, to determine the prevalence and clinical characteristics of a unique disorder of the entheses (tendons, ligaments, and joint capsules). We found a generalized involvement of the entheses, with exuberant calcification of tendon and ligament insertions and of joint capsules, in 69 per cent of the subjects. The prevalence and extent of disease increased with age but were not correlated with sex. Commonly affected sites included the hand and sacroiliac joints. Histologic evaluation in a selected patient revealed intratendinous lamellar bone but no inflammatory cells. Our observations indicate that this disorder is an integral part of X-linked hypophosphatemic osteomalacia and exhibits clinical, radiographic, and histologic characteristics that differentiate it from degenerative disorders of these tissues and seronegative spondyloarthropathies.

The use of radiolabeled and fluorescein-labeled antiglobulins in assays to predict platelet transfusion outcome.

We used both radiolabeled and fluorescein-labeled antiglobulins in assays to detect antibodies against platelets in multiply transfused patients to determine the value of these tests in predicting the outcome of platelet transfusion in such patients. In 15 allosensitized patients, we studied 68 single-donor platelet transfusions, 43 (63%) of which had a poor outcome, defined as a corrected count increment (CCI), less than 10,000. The results obtained with either test were significantly correlated with the CCI following transfusion (p less than 0.001), but the assay using the radiolabeled antiglobulin had slightly better sensitivity, specificity, and predictive value. When the assays were used in combination, there was again significant correlation with the CCI of the transfusion, p less than 0.001. When both assays predicted failure of the transfusions, 31/31 (100%) such transfusions resulted in a CCI of less than 10,000, and when both assays predicted success of the transfusions, 14/15 (93%) such transfusions resulted in a CCI of greater than 10,000. Both assays are useful in predicting the outcome of the platelet transfusions; when the assay results were concordant, almost total predictive accuracy was obtained.

Three new phenotypes of human red cell acid phosphatase: ACP1FA, ACP1GA, and ACP1GB.

Three new phenotypes of human erythrocyte acid phosphatase (ACP1) have been detected and found to be unique by direct comparison with previously identified ACP1 variants. One of these new electrophoretic variants, labeled as ACP1FA, has been detected in the Hispanic population of California. The electrophoretic variants identified as ACP1GA and ACP1GB have been detected in a black family in North Carolina. A family study has shown that ACP1G is transmitted as an allele of ACP1.

Application of probability of paternity calculations to an alleged incestuous relationship.

An alleged case of incest between half siblings has been examined by standard blood grouping and human leukocyte antigen (HLA) serology. The data were analyzed statistically using single and joint possibilities of paternity. The existence of the alleged relationship between the two parties in question is quite probable.

A feasibility study of human leukocyte antigen (HLA) typing for dried bloodstains.

This paper constitutes a feasibility report on the use of the human leukocyte antigen (HLA) system for the typing of dried bloodstains. Antigens tested include the HLA-A2, A3, A10, B7, B8, and B14 alleles. An aging study conducted on A3 positive bloodstains showed that HLA-A3 could be reliably detected on bloodstains stored up to 30 days at 22 degrees C. Unlike most earlier reports on HLA typing of bloodstains, no cross-reactivity problems were detected with the antisera used in this study. In addition to the successful typing of bloodstains, we were also able to type fresh, neat seminal and saliva stains in the A2 and A10 antigenic systems.

HLA-B15 association with erythema multiforme.

Erythema multiforme (EM) is a cutaneous reaction pattern which follows numerous infections, drugs, neoplastic and inflammatory disorders in some individuals. We undertook a prospective study of thirty-eight HLA specificities of the -A, -B, and -C series in 16 Caucasian patients with EM and in 140 local Caucasian controls. Seven of 16 patients (44%) with EM and 5 of 9 patients (55%) with EM following herpes simplex infections possessed the HLA-B15 antigen, compared to 7% of local controls and 11.6% of the 1980 WHO Workshop Caucasian controls. Both associations were highly significant (p = 0.0125 and p = 0.02) when corrected for 38 HLA antigens. This is the first reported HLA association for erythema multiforme, a disease which may be a host-specific immune response to various antigens, determined in part by genes linked to HLA-B15.

Lack of association between Alzheimer's disease and histocompatibility antigens.

The present report describes the distribution of histocompatibility antigens in 52 patients with Alzheimer's disease. No significant associations were observed between this illness and particular HLA types before or after statistical correction for multiple comparisons. These findings are discussed in terms of the difficulties inherent in the clinical diagnosis of Alzheimer's disease and with regard to the choice of suitable control populations.