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Public trust in medical institutions is essential for ensuring compliance with medical directives. However, the politicization of public health issues and the polarized nature of major news outlets suggest that partisanship and news consumption habits can influence medical trust. This study employed a survey with 858 participants and used regression analysis to assesses how news consumption habits and information assessment traits (IATs) influence trust in medical scientists. IATs included were conscientiousness, openness, need for cognitive closure (NFCC), and cognitive reflective thinking (CRT). News sources were classified on the basis of factuality and political bias. Initially, readership of liberally biased news was positively associated with medical trust (p < 0.05). However, this association disappeared when controlling for the news source’s factuality (p = 0.28), while CRT (p < 0.05) was positively associated with medical trust. When controlling for conservatively biased news sources, factuality of the news source (p < 0.05) and NFCC (p < 0.05) were positively associated with medical trust. While partisan media bias may influence medical trust, these results suggest that those who have higher abilities to assess information and who prefer more credible news sources have a greater trust in medical scientists.

Background: Ototoxicity (hearing loss, tinnitus and/or vertigo) is a serious adverse event of cisplatin treatment in children with cancer. The heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. This study investigated the association between carriership of novel single nucleotide polymorphisms (SNPs) and cisplatin-induced hearing loss (CIHL) in childhood cancer patients.Material and methods: The discovery cohort included cisplatin treated, non-cranial irradiated pediatric cancer patients within the European PanCareLIFE (PCL) study (N=390). CIHL at end of cancer treatment was defined as Muenster grade >=2b, assessed by pure tone audiometry. DNA was genotyped using the Infinium© Global Screening Array. Logistic regression models were applied including age at diagnosis, sex, cisplatin total cumulative dose and principal components 1-4, assuming an additive effect of the minor allele. Replication of the findings was performed in two independent, similarly treated cohorts (N=192 and N=188). Functional validation experiments in cultured human HeLa cell lines were performed to determine the effect of knockdown of the SNPs nearest identified gene on cisplatin-induced toxicity.Results: In the PCL discovery cohort, 8 SNPs reached a suggestive significance of P

Aims: Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies.Methods: PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohort and case-control studies, a longitudinal study and an intervention study. Ethics and data protection issues have been taken into account from the beginning.Results: PanCareLIFE will investigate the way that treatment impairs female fertility, by evaluating anti-Mullerian hormone levels and the underlying genetic susceptibility to loss of fertility. For our fertility studies, more than 6000 survivors have completed questionnaires, more than 1500 provided serum samples and more than 400 case-control triads have been identified. Fertility preservation guidelines for boys and girls will be developed. More than 2000 survivors have contributed audiograms for the ototoxicity study. Almost 1000 samples were sent for genetic analysis related to ototoxicity and gonadal reserve. The SF-36 questionnaire will measure quality of life in more than 10,000 survivors.Conclusions: The large number of subjects enrolled in PanCareLIFE and the detailed information accumulated will allow in-depth evaluation of important outcomes. Fertility preservation guidelines will help patients and their families make informed decisions and contribute to their long-term well-being. (C) 2018 Elsevier Ltd. All rights reserved.

Das Antiandrogen Flutamid ist ein in der Behandlung des fortgeschrittenen Prostatakarzinoms haufig eingesetztes Medikament. Eine klinisch relevante Hepatotoxizitat wird selten beobachtet, kann aber unter Umstanden todlich verlaufen. Wir berichten uber 2 Patienten mit Prostatakarzinom, bei denen es unter der Therapie mit Flutamid zu einem toxischen Leberparenchymschaden unterschiedlichen Ausmases gekommen war. Nach Absetzen der entsprechenden Medikation und Gabe von Kortikosteroiden kam es bei einem Patienten zur vollstandigen Ruckbildung der klinischen Symptome und der laborchemischen Veranderungen. Bei dem anderen Patienten zeigte sich auch nach Absetzen der Medikation ein schwerer Verlauf mit zunehmender Leberdysfunktion und Entwicklung eines hepatorenalen Syndromes, sodass der Patient schlieslich im Leberzerfallskoma verstarb. Es handelt sich hierbei um den unseres Wissens ersten flutamidassoziierten Todesfall in Deutschland. Die in der Literatur verfugbaren Daten zum Arzneimittelmetabolismus und die bisher publizierten Falle werden aufgefuhrt.

HISTORY AND CLINICAL FINDINGS A 72-year-old woman, who suffered from increasing dyspnea and productive cough was admitted to hospital. Clinical examination revealed a reduced respiratory sounds over the left lung and a painless and unmovable tumor in the area of the left hip. CLINICAL AND LABORATORY TESTS Apart from hypoxemia (pO2 7.81 kPa) the laboratory values did not indicate any pathological findings. The X-ray and CT-scan of the chest showed a few spotty shadows and pleura effusion on the left. No tumor cells were detected in the pleural effusion. In biopsies of the visceral and parietal pleura as well as biopsy within the tumor in the area of the left hip there were clusters of tumor cells of a granular cell tumor. DIAGNOSIS, TREATMENT AND CLINICAL COURSE Because the same tumor cell type was detected in the visceral and parietal pleura and wihtin the tumor at the left gluteus area, we diagnosed a malignant granular cell tumor. The CT-scan was suspicious of lung metastasis. The primary tumor was located in the area of left hip. The patient was in a poor general condition and she suffered from an extensive metastastic disease; curative treatment was not possible. A pleurodesis was performed. The patient died nine months after initial diagnosis. CONCLUSION A rare malignant granular cell tumor was discovered by detecting tumor tissue of granular cell tumor in the pleura and within a tumor in the left gluteus area. Another indication of a metastatic disease were multifocal lesions in the lung detected by CT-scan. Curative treatment was not possible.

Electrical engineers play an important role in developing new tools to enhance the creative process. One of the most creative tools ever developed was the computer. Anyone can create art, music, or literature using a computer and the many software tools on the market. Of course, not all creations are equal. Just because the computer spits out the creation doesn't mean it's good. Spelling and grammar checkers make many documents more readable but these tools certainly don't transform them into works of art. Can a computer actually improve a work of art? Improving is synonymous with optimizing. Optimization implies that some inputs to an experiment, model or mathematical function can be varied so that the outcome or result is the best it can be. What better optimization tool to use for the creative process than one that is based on natural selection-the genetic algorithm (GA). Genetic algorithms mimic nature by combining genetics and natural selection on a computer to find optimum solutions. They have proven useful in areas ranging from stock market analysis to satellite design. These algorithms are relatively easy to understand. To demonstrate their power and versatility for enhancing creativity, we use a genetic algorithm to create art and music with the help of human input.

The electronic properties of a two-dimensional array of anisotropic parabolic quantum dots in the presence of a quantizing magnetic field are investigated in the tight-binding approximation. The mini-bands strongly depend on the superlattice periods, the eccentricity of the anisotropic parabolic quantum dot and the magnetic field. The electron-phonon interaction renormalizes the gaps between the mini-bands, their widths and results in a resonant level splitting.

Mechanisms for human membranous glomerulonephritis (MGN) remain elusive. Most up-to-date concepts still rely on the rat model of Passive Heymann Nephritis that derives from an autoimmune response to glomerular megalin, with complement activation and membrane attack complex assembly. Clusterin has been reported as a megalin ligand in immunodeposits, although its role has not been clarified. We studied renal biopsies of 60 MGN patients by immunohistochemistry utilizing antibodies against clusterin, C5b-9, and phosphorylated-protien kinase C (PKC) isoforms (pPKC). In vitro experiments were performed to investigate the role of clusterin during podocyte damage by MGN serum and define clusterin binding to human podocytes, where megalin is known to be absent. Clusterin, C5b-9, and pPKC-alpha/beta showed highly variable glomerular staining, where high clusterin profiles were inversely correlated to C5b-9 and PKC-alpha/beta expression (P=0.029), and co-localized with the low-density lipoprotein receptor (LDL-R). Glomerular clusterin emerged as the single factor influencing proteinuria at multivariate analysis and was associated with a reduction of proteinuria after a follow-up of 1.5 years (-88.1%, P=0.027). Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment. Preliminary in vitro experiments showed podocyte binding of biotinilated clusterin, co-localization with LDL-R and specific binding inhibition with anti-LDL-R antibodies and with specific ligands. These data suggest a central role for glomerular clusterin in MGN as a modulator of inflammation that potentially influences the clinical outcome. Binding of clusterin to the LDL-R might offer an interpretative key for the pathogenesis of MGN in humans.

Flutamide is an antiandrogen and frequently used for the treatment of prostatic cancer. Severe hepatotoxicity occurs in few patients but may be fatal. We report on two patients with prostatic cancer who received a therapy with flutamide. They showed different degrees of liver damage. One patient recovered completely after withdrawal of Flutamide under medication with steroids. Clinical symptoms and laboratory findings returned to normal within four weeks. Despite immediate withdrawal of Flutamide, the other patient showed a severe course with progressive liver dysfunction and hepatorenal syndrome. He finally died under the clinical picture of fulminant hepatic coma. This case represents the first death associated with flutamide in Germany. The literature concerning the metabolism of flutamide and the published cases of hepatotoxicity of this drug are reviewed.

Communications antennas on spacecraft are usually circularly polarized. As the spacecraft maneuvers, its antenna and the ground station antenna may not point directly at each other. Antennas not properly aligned for optimal power transfer usually create a polarization mismatch and a loss in transferred power. In this paper, a scheme for compensating for polarization mismatch is considered using crossed dipoles. One of the crossed dipole's amplitude and phase is adjusted using numerical optimization, and the Numerical Electromagnetic Code generates the electromagnetic response. Optimizing only for circular polarization produces losses in radiated power that offset the polarization correction. The polarization optimization may improve power transferred when the spacing between the orthogonal dipoles is increased. The next step modified the optimization process to consider power transferred. With this improvement, the power transferred always increased up to a maximum of 2.0 dB at /spl theta/ = 80/spl deg/. Using adaptive crossed dipoles at the transmitter and receiver was also considered and further improved the model.

We study the effect of the interaction of electrons confined in one spatial direction in a parabolic quantum well with longitudinal optical (LO) phonons in a tilted magnetic field. In detail we analyse the polaron cyclotron mass, calculated using second-order perturbation theory, in dependence on the magnetic field strength and the tilt angle of the magnetic field. We find a strong dependence of the cyclotron masses on the tilt angle, corresponding to the two measurable transitions in cyclotron resonance experiments.

The aim of our study was to investigate the coexistence of autoimmune diseases (autoimmune thyroid disease and type 1 diabetes mellitus, T1DM) in patients affected by Juvenile Chronic Arthritis (JCA).We studied 66 patients affected by JCA, 42 females and 24 males: 42/66 patients had a pauciarticular form of JCA, 13/66 had a polyarticular form and 11/66 had a systemic form. All the patients underwent autoimmune thyroid screening through determination of anti-thyroglobulin (TgA) and anti-peroxidase (TPOA) autoantibodies. Patients with TgA and/ or TPOA, underwent thyroid sonography. T1DM screening included determination of anti-glutamic acid decarboxylase (GADA), anti-insulin (IAA), anti-tyrosine phosphatase-like protein (IA-2A) and anti-islet cell (ICA) autoantibodies. Oral glucose tolerance test (OGTT) was performed only in patients with autoantibody positive values. HLA typing for risk of T1DM was performed in 43 patients.Nine female patients (14%) showed anti-thyroid autoantibodies, in particular: TgA in 3 cases, TPOA in 5, TgA and TPOA in only 1. In 3 of these patients, ultrasound examinations showed thyroid abnormal pattern, suggesting Hashimoto's thyroiditis. As regards T1DM, only 2 patients showed positive levels of GADA. As regards HLA typing, one or more T1DM susceptibility heterodimers were detected in 20 patients (46%) (13 with 1 heterodimer, 7 with 2 heterodimers).Our study showed that anti-thyroid autoantibody frequency (9/66, 14%) was higher in JCA than in the general population, while T1DM markers (islet autoantibodies and genetic markers) were not frequent. These results suggest to investigate specific markers of thyroid autoimmunity in patients with JCA, in particular in females with JCA pauciarticular form.

A 72-year-old woman, who suffered from increasing dyspnea and productive cough was admitted to hospital. Clinical examination revealed a reduced respiratory sounds over the left lung and a painless and unmovable tumor in the area of the left hip.Apart from hypoxemia (pO2 7.81 kPa) the laboratory values did not indicate any pathological findings. The X-ray and CT-scan of the chest showed a few spotty shadows and pleura effusion on the left. No tumor cells were detected in the pleural effusion. In biopsies of the visceral and parietal pleura as well as biopsy within the tumor in the area of the left hip there were clusters of tumor cells of a granular cell tumor.Because the same tumor cell type was detected in the visceral and parietal pleura and wihtin the tumor at the left gluteus area, we diagnosed a malignant granular cell tumor. The CT-scan was suspicious of lung metastasis. The primary tumor was located in the area of left hip. The patient was in a poor general condition and she suffered from an extensive metastastic disease; curative treatment was not possible. A pleurodesis was performed. The patient died nine months after initial diagnosis.A rare malignant granular cell tumor was discovered by detecting tumor tissue of granular cell tumor in the pleura and within a tumor in the left gluteus area. Another indication of a metastatic disease were multifocal lesions in the lung detected by CT-scan. Curative treatment was not possible.

Twelve paediatric patients with aplastic anaemia and two groups of normal control subjects underwent flow cytometric analysis for intracytoplasmic expression of gamma interferon (gamma-IFN) and tumour necrosis factor alpha (TNF-alpha) in bone marrow and peripheral blood CD4+ and CD8+ cells. The same cytokines were tested, by immunoassay, in culture supernatants from unstimulated bone marrow mononuclear cells (MNCs). Marrow CD4+ and CD8+ cells expressing gamma-IFN and TNF-alpha were significantly increased in the patients in comparison with normal control subjects (P from0.05 to0.0001 in the different cellular subsets). Patients' marrow CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were significantly increased when compared with the same cell fractions from paired peripheral blood samples (P from0.05 to0.0001 in the various cellular subsets). In the supernatant of marrow MNCs, gamma-IFN and TNF-alpha were detected in four out of eight and five out of eight cases, respectively, whereas neither cytokine was traceable in the control subjects. Patients' peripheral blood CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were not significantly increased in comparison with those from normal control subjects. Whereas patients with favourable and unfavourable outcomes had no significantly different proportions of marrow gamma-IFN+/CD4+ and gamma-IFN+/CD8+ cells, the percentages of marrow CD4+ and CD8+ cells containing TNF-alpha were significantly lower in subjects with favourable than in those with unfavourable outcome. Overall, these findings show that, in aplastic patients, T cells overexpressing gamma-IFN and TNF-alpha concentrate in the bone marrow and that intracytoplasmic expression of TNF-alpha in marrow CD4+ and CD8+ cells is associated with an unfavourable clinical course.

We carried out a retrospective study on the infection rate--in episodes per 100 person months at risk (p/m/r)--of septicaemia and invasive mycoses in children with solid tumours treated at a single institution between 1985 and 1996. Among 982 patients, accounting for 8108 p/m/r, 257 infectious episodes were documented, for an infection rate of 3.2. The infection rate for "intensive" treatment was greater than that for "less intensive" treatments, 3.7 compared with 0.5, respectively; P0.001. 58% of infectious episodes were associated with neutropenia, 22% were megatherapy-related, and 39% were related to central venous catheter (CVC), while in 13% of the episodes no risk factor was identified. Of the episodes, single organism Gram-positive bacteraemias accounted for 62%, single organism Gram-negative for 23%, multiple organism bacteraemias for 7%, invasive mycoses for 4%, and isolated fungaemias for 4%. The infection rate for Gram-positive organisms decreased significantly over time (-5.9% per year; P0.01), but increased for the Gram-negative organisms (+3.4% per year; P=0.4). This study demonstrates that the risk of bacteraemia increases in parallel with the treatment intensity, and that a considerable number of children with solid tumours develop bacteraemia in the absence of an identifiable risk factor.

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable confidence for twins monozygosity assessment, we termed these pairs 'presumed monozygotic' (pMZ). Nine families had more than one affected relative: five with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins (one pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identification of LCH in siblings and first cousins from known or possibly consanguineous families, and with prior reports of three affected parent-child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.

ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma developed severe invasive pulmonary aspergillosis during a state of leucopenia after chemotherapy.The initial manifestation was an infiltration in the right upper lobe of the lung, identified by lung scintigraphy as a peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage extreme high titre of Aspergillus antigen were seen as a laboratory indication of an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly isolated from bronchoalveolar lavage and bronchial secretion.Treatment was started with amphotericin B plus 5-flucytosine together with repeatedly bronchoscopic instillation of miconazole followed by thoracosurgical intervention with resection of the right upper lobe of the lung. Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred three months later probably due to persistence of aspergillus fungal elements in the left lung. The aspergillosis relapse was treated at first with liposomal amphotericin B. After eighteen days of treatment this was changed to a combination of 5-flucytosine with oral application of itraconazole, and cure was achieved.

To estimate the risk of secondary leukemias after treatment with etoposide (VP-16), we evaluated subjects treated for Langerhans' cell histiocytosis (LCH) according to cooperative protocols in Italy or in Austria, Germany, Holland and Switzerland (AGDS). For each subject, information was collected on the cumulative dosages of chemotherapy and radiotherapy received, vital status and occurrence of secondary leukemia. The expected number of leukemias was estimated using age-specific incidence rates from the cancer registries in Italy and Germany. Standardized incidence ratios (SIR) were used to measure the risk of secondary leukemia among LCH patients. Five leukemias occurred among the 241 Italian study patients (SIR 520), whereas no cases were reported among the 363 AGDS patients. Interestingly, and in contrast to previous descriptions of epipodophyllotoxin-related leukemias which are mostly FAB M4 or M5, these leukemias showed typical FAB M3 features, and received a dose of VP-164,000 mg/m2. Among the AGDS cohort, very few subjects were exposed to high doses of VP-16. The risk of secondary acute non-lymphoblastic leukemia (s-ANLL) among the Italian subjects exposed to VP-16 was more than 1,000 times greater than expected. The study suggests that high doses of VP-16 appear to increase the risk of s-ANLL in LCH patients. The fact that all the leukemias described in the Italian LCH cohort were promyelocytic, and evidence of a higher incidence of promyelocytic leukemias among Italians and Latinos, suggest that high doses of etoposide in subjects of Latino origin may lead to aberrations on chromosomes 15 and 17.

Chromosomal aberrations involving the chromosomal breakpoint region 12q14-15 are frequently seen in a variety of mesenchymal tumors as uterine leiomyomas, lipomas, myxoid liposarcomas, enchondromas, or hemangiopericytomas. Therefore, this breakpoint region seems to be one of the most frequent chromosomal abnormality associated with the initiation of human mesenchymal neoplasms. To narrow down the breakpoint region on a molecular level in cells of three pulmonary chondroid hamartomas with 12q14-15 aberrations, we performed fluorescence in situ hybridization analysis with different cosmid clones originating from a YAC and cosmid contig overspanning parts of the region 12q14-15. We were able to narrow down the breakpoint to a region of 175 kb belonging to an area designated multiple aberration region because it also includes the breakpoints of leiomyomas, lipomas, and pleomorphic adenomas with 12q14-15 abnormalities. Our molecular and cytogenetic data suggest that hamartomas of the lung molecularly belong to the benign group of mesenchymal tumors showing multiple aberration region involvement.

Cytogenetic techniques were used to study the tissue involved in neural tube defects. Eighteen patients have been evaluated and no specific alterations have been detected. We conclude that, whatever are the mechanisms that lead to neural tube defect, their origins must be searched for at the molecular level.

To determine the impact of treatment on scholastic performance in the first cohort of survivors of childhood acute lymphoblastic leukemia who are old enough to have completed their educational experience.Retrospective cohort study.Twenty-three institutions in the Childrens Cancer Group.A total of 593 adult survivors of childhood acute lymphoblastic leukemia and 409 sibling controls.Enrollment in special programs, grades during high school, graduation from high school, college admission, and college graduation.After diagnosis, survivors were more likely than their sibling controls to enter a special education (relative risk [RR] = 3.4; P.01) or a learning disabled (RR = 3.6; P.01) program, while just as likely to enter gifted and talented programs (RR = 1.0). The risk associated with special education and learning disabled programs increased with increasing dose of cranial radiotherapy. Despite these problems, survivors generally had the same probability as their siblings of finishing high school, entering college, and earning a bachelor's degree. However, survivors treated with 24 Gy and those diagnosed before 6 years of age were less likely to enter college (RR = 0.67 and 0.6, respectively; P.01).This large study demonstrates that childhood acute lymphoblastic leukemia survivors have a greater likelihood of being placed in special education or learning disabled programs than their siblings, but that most are able to overcome these problems. Dose of cranial radiotherapy and age at diagnosis are the most important education-related risk factors.

This study aims at defining the frequency and severity of late effects in a series of 288 long-term survivors of childhood cancer treated from 1962 to 1982 at the Giannina Gaslini Children's Research Hospital of Genoa, Italy.All cases with a diagnosis of malignancy in childhood and a minimum of 2.5 years from discontinuation of treatment were considered eligible. For all cases the study included physical, endocrinological, and psychological examination. Groups of patients selected according to treatment underwent cardiac, pulmonary, orthopedic, and ophthalmologic evaluation. The sequelae observed were scored according to a grading system in which asymptomatic subclinical defects are distinguished from those that are sufficiently symptomatic to require some type of corrective measure.Overall, 200 of 288 cases (69.4%) presented with some kind of abnormality. Symptomatic changes were present in 92 cases (42%); in these, severe and life-threatening late toxicity was reported in 61 (21.2%) and 12 cases (4.2%), respectively. The major risk factors appeared to be irradiation, type of tumor, and whether the patient had received therapy before 1974.In our experience, this study demonstrates that there was a true excess of morbidity caused by the disease and its treatment in long-term survivors from almost any kind of childhood cancer. It also sheds light on how to prevent, diagnose, and adequately treat these patients and proposes specific criteria for the evaluation of the severity of delayed toxicity in long-term survivors of cancer in childhood.

A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

Infantile leukemia is a rare disorder, and few cytogenetic studies have been performed on this condition.The authors present the cytogenetic analyses performed on 14 cases of infantile leukemia. The most frequent chromosomal changes are rearrangements involving 11q (4 cases) and gains of one or more chromosomes 21. Patients with chromosomal rearrangements show a worse prognosis than those with only hyperdiploidy or a normal karyotype, although the difference was not statistically significant due to the small size and short median follow-up.

Carcinomas were induced to the thyroid gland of female rats, using a method originally proposed by Thomas and Bollmann (metachronous application of nitrosomethylurea and methylthiouracil), to establish cytomorphological, histomorphological, cytochemical, and flow-cytophotometric criteria for diagnosis of thyroid carcinoma. Verification was also intended of the diagnostic value of each of the methods involved for differentiation of nodular goitre. Another purpose of the study was to find out, whether chemically induced thyroid tumours in rat were comparable to thyroid neoplasms in man. This provided to the examiners genetically coherent and morphologically comparable biological material at various stages of thyroid tumour growth which included diffuse and adenomatous hyperplasias, adenomas, and, from the 18th to 42nd experimental weeks, papillary as well as follicular carcinomas in 31 to 100% of all experimental animals involved. Cytomorphological comparability of rat thyroid material (imprint specimens) with human material (fine-needle aspiration cytology) was ensured for normal as well as for hyperplastically altered thyroid glands, including adenomatous and carcinomatous changes. Hence, group typing of thyroid cytology, originally devised for human specimens, could be easily adapted to material obtained from rat. Assessment of cytological samples by microscopic criteria yielded an accuracy of 89% in malignoma diagnosis and proved to be an approach of highly informative potential also in the context of rat experiments. Use of additional cytochemical techniques (PAS, toluidine-blue, peroxidase, alkaline and acid phosphatases, gamma-glutamyl transpeptidase) as well as quantitative DNA determination by means of flow-cytophotometry was helpful in casting light at some scattered trends of change from normal for certain stages of proliferation, but it failed to enhance information in cytomorphological diagnosis of the individual case.

The punctates of the biochemical joint function test contain hydroxyethyl starch which disturbs the assay of uronic acid and glucosamine for the estimation of hyaluronate. Therefore hyaluronate (0.03-0.75 g/l) was estimated by precipitation with Alcian blue on cellulose acetate membranes and measuring of the absorbance at 678 nm after dissolution in aqueous SDS (75 g/l). The gel-filtration HPLC separates the high-molecular-mass hyaluronate from low-molecular-mass impurities of biological samples. By comparing with a standard curve (0.5-2.5 g/l hyaluronate) the concentration can be determined. The results obtained by the two methods were significantly correlated (p less than 0.05). The Alcian blue technique is useful for rapid screening, the HPLC technique to confirm these values.