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  • 1
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Sur 258 patients opérés pour hyperparathyroïdie secondaire (HPT II) entre 1971 et 1988, 33 ont eu une ou plusieurs réinterventions pour HPT II persistante ou récidivante. Ces réinterventions n'ont été suivie ni d'une mortalité ni d'une morbidité significative. Après parathyroïdectomie incomplète (25 cas), 15 patients ont été réopérés. Douze d'entre eux avaient déjà été opérés dans un autre établissement. Trois patients sont morts pour des causes sans rapport avec leur HPT II. Les 12 autres patients sont guéris. Après parathyroïdectomie subtotale réussie (79 cas), 2 patients (2.5%) ont eu une récidive, respectivement 5 et 6 ans plus tard. Actuellement les 2 patients sont guéris. Après parathyroïdectomie totale avec autotransplantation (152 cas), 16 patients (10.5%) ont dû être réopérés á cause des greffons. Le délai moyen avant la réintervention fut de 2 1/2 ans. Une hypertrophie des fragments greffés fut observés dans 4 cas (2.6%) mais 2 seulement de ces 4 patients ont été guéris après ablation des greffons. Chez 5 patients du tissu parathyroïdien résiduel ou une glande surnuméraire au cou ou dans le médiastin ont été suspectés, mais ceci n'a pas été confirmé: un patient a été à nouveau cervicotomisé sans succès, un autre refuse toujours la réopération, et 3 sont morts. Chez 6 autres patients la récidive était discutable et l'HPT II n'a pas été confirmée. Quant aux 3 derniers patients, le diagnostic était incorrect et une intoxication à l'aluminium fut démontre utérieurement. Les résultats d'une réintervention pour HPT II persistante ou récidivante dépendent avant tout d'un bon diagnostic. Après parathyroïdectomie subtotale réussie, les réinterventions sont rares et simples. Après parathyroïdectomie totale et transplantation, on ne doit pas oublier que les récidives peuvent survenir sur les greffons et/ou sur le tissu résiduel au cou ou au médiastin.
    Abstract: Resumen Entre 258 pacientes operados por hiperparatiroidismo secundario (HPT II) entre 1971 y 1988, un total de 33 tenían historia de una o más reoperaciones por HPT II persistente o recurrente. Estas operaciones no produjeron mortalidad ni morbilidad significativa. De 25 pacientes con paratiroidectomía inadecuada, 15 pacientes fueron reoperados. Doce habían sido operados inicialmente en otra institución. Tres murieron por causas no relacionadas con su HIPT II; los otros 12 pacientes se encuentran libres de enfermedad. De 79 pacientes sometidos a paratiroidectomía subtotal exitosa, 2 (2.5%) tuvieron recurrencia a los 5 y 6 años, respectivamente. Actualmente los 2 están libres de enfermedad. De 152 pacientes sometidos a paratiroidectomía con autotrasplante, 16 (10.5%) requirieron reoperaciones sobre los injertos. El promedio del intervalo a la reoperación fue de 2 1/2 años. Se observó hipertrofia de los fragmentos injertados en 4 casos (2.6%), pero sólo 2 fueron curados con la remoción de los injertos. Se sospechó la presencia de tejido paratiroideo residual o de una glándula supernumeraria ubicada en el cuello o en el mediastino en 5 casos, pero ésto no pudo ser confirmado puesto que uno ya había sido reoperado sobre el cuello sin éxito, otro aún rehusa operación, y 3 han muerto. En otros 6 pacientes, la recurrencia apareció dudosa y el HPT II no pudo ser confirmado. El diagnóstico fue incorrecto en los últimos 3 pacientes, y en ellos se comprobó, más tarde, intoxicación por aluminio. Los resultados de la reoperación por HPT II dependen, en primer lugar, de un diagnóstico correcto. Después de paratiroidectomia total y trasplante, debe tenerse en cuenta que las recurrencias pueden presentarse en el trasplante y/o el tejido residual en el cuello o el mediastino.
    Notes: Abstract Among 258 patients operated on for secondary hyperparathyroidism (HPT II) from 1971 to 1988, a total of 33 had one or more reoperations for persistent or recurrent HPT II. These reoperations did not induce any mortality or significant morbidity. After inadequate parathyroidectomy (25 cases), 15 patients were reoperated. Twelve of these had undergone initial surgery at another institution. Three patients died of causes unrelated to their HPT II. The other 12 patients are disease-free. After successful subtotal parathyroidectomy (79 cases), 2 patients (2.5%) had a recurrence 5 and 6 years later, respectively. Currently, the 2 patients remain disease-free. After total parathyroidectomy with autotransplantation (152 cases), 16 patients (10.5%) had reoperations on the grafts. The mean time before reoperation was 2 1/2 years. Hypertrophy of grafted fragments was observed in 4 cases (2.6%), but only 2 of these 4 patients were cured by removal of the grafts. Residual parathyroid tissue or a supernumerary gland in the neck or the mediastinum was suspected in 5 patients, but this could not be confirmed because one had already been reoperated on in the neck without success, another still refuses reoperation, and 3 died. In 6 other patients, the recurrence was debatable and HPT II was not confirmed. In the last 3 patients, the diagnosis was incorrect and aluminium intoxication was proved later. Results of reoperations for persistent or recurrent HPT II depend, first, on a correct diagnosis. After Successful subtotal parathyroidectomy, reoperations are rare and simple. After total parathyroidectomy and transplantation, it must be kept in mind that recurrences can occur on the grafts and/or on residual tissue in the neck or mediastinum.
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  • 2
    ISSN: 1432-5233
    Keywords: Insulin-dependent diabetes ; Islet cell antibodies ; Complement-fixing ICA ; C-peptide ; Geographical variation ; Seasonal variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3–4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference in incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden (‘North’) and Pittsburgh were younger (〈10 years old) at diagnosis compared with those in the other clinics in Europe (P〈0.05 versusP〈0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (〈8 days;P〈0.001) and higher blood glucose (〉20 mmol/l;P〈0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%;P〈0.01) or in France (70%;P〈0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (〈0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis, showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.
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  • 3
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; children ; HLA-types ; heterogeneity symptoms at onset ; partial remission ; genetic susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The presence of HLA-DR 3 was analysed in 745 patients with Type 1 (insulin-dependent) diabetes with age at diagnosis between 1–19 years. HLA-DR 3 and/or 4 was found in 678/745 (91%) of the patients. Presence of DR 2 with neither DR 3 nor 4 was demonstrated in 15 patients. Patients with HLA-DR 3 without DR 4 presented with Type 1 diabetes more evenly over the year; they also presented without incidence peaks at 7 years or 10–11 years, as seen especially in DR 3/4 patients. The DR 3 patients more often had mild disease with less ketonuria at diagnosis, less often ketoacidotic symptoms and more often a subsequent partial remission. The apparently more severe disease among diabetic girls may, at least to some extent, be explained by their higher prevalence of HLA-DR4. The differences found were similar in North America and Europe. The results suggest that Type 1 diabetes is a genetically heterogenous disease and that HLA-typing may be a useful marker of this heterogeneity.
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  • 4
    ISSN: 1432-0428
    Keywords: Prediction ; Type 1 (insulin-dependent) diabetes ; autoimmunity ; autoantibodies ; prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic determination as well as prospective analysis of islet cell autoantibodies and autoantibodies to insulin were conducted in a population of 479 first degree relatives of 174 Type 1 (insulin-dependent) diabetic patients. Analysis of HLA haplotypes within families illustrated the high frequency of DR3 and DR4 alleles with preferential transmission from parent to both affected and unaffected offspring. DR4 was preferentially associated with DQw3.2 (TA10−) in 60/73 (82.2%) patients and 101/127 (79.5%) relatives. Relatives have been followed for a period of 800 subject-years. Twenty-two out of 430 relatives (5.1%) were found islet cell antibodies (ICA-IgG) positive. Seven sera with low titres became negative 6 months later at two different determinations. Fifteen sera ICA-IgG and ICA-protein A positive with high titres remained positive thereafter. Half of the ICA positive relatives were also found insulin autoantibodies (IAA) positive. All but 3 ICA negative relatives did not have IAA in their sera. Analysis of IAA specificity with competition experiments indicated that most antibodies recognised epitopes shared between human and pork insulins while four were specific for human insulin determinants. Analysis of class I and class II HLA antigen distribution indicated no particular allelic restriction in antibody positive individuals. Metabolic status of antibody positive relatives was determined with oral and intravenous charge of glucose. Two haplo-identical DR3-DQw2 brothers became diabetic during the study. One child and one mother both with DR4-DQw3.2 became intolerant to glucose. Each of these relatives had high titre ICA prior to metabolic deterioration. Taken together, these data indicated that ICA and IAA may be present in first degree relatives of diabetic patients. Individualisation of markers of the ongoing autoimmune process and accurate evaluation of the residual B-cell mass are necessary steps before further immune interventions in the early phases of the disease.
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  • 5
    ISSN: 1432-0428
    Keywords: Islet cell autoantibodies ; Type 1 (insulin-dependent) diabetes mellitus ; first degree relatives ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Factors associated with diabetes onset were analysed for their predictive value in 708 first-degree relatives of Type 1 (insulin-dependent) diabetic patients including 374 parents and 308 siblings of Type 1 diabetic patients. Relatives were prospectively followed for 2 304 subject years with blood samples for specific autoantibody evaluation. Islet cell cytoplasmic autoantibody titres were quantified in Juvenile Diabetes Foundation units with a threshold of positivity of 5 units. Insulin autoantibodies were determined using Tyr-A14 iodinated human insulin. HLA typing was performed in 92% of the relatives. During the time of study, 17 of 646 (2.6%) relatives showed islet cell antibodies. During follow-up, eight relatives developed diabetes, including six with high islet cell antibody titre. Taking titres above 20 units increased the positive predictive value from 35% to 75% whereas the presence of insulin autoantibodies did not increase the positive predictive value for the disease. Analysis of metabolic profiles months before the onset of diabetes by either oral or intravenous glucose loads, indicated a considerable level of heterogeneity with relatives with a high islet cell antibody titre who rapidly developed insulin-dependent diabetes, whereas others remained insulin-independent during the same observation period despite comparable titres. This study clearly indicates that initial islet cell antibody titre is not sufficient to predict individual outcome. Follow-up samples are clearly needed to monitor progression of the disease. Few relatives with persistent immunologic positivity progress to clinical Type 1 diabetes, suggesting that non-progressive and sub-clinical Beta-cell dysfunction is common. Despite current knowledge and available genetic and immune markers, early identification of the relatives progressing to clinical diabetes is still difficult and does not allow at the present time aggressive immunointervention at the prediabetic stage.
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  • 6
    ISSN: 1432-0428
    Keywords: Dawn phenomenon ; Type 1 (insulin-dependent) diabetes ; adolescent ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3±0.7 mmol/l at 01.00 hours to 7.1±1.1 mmol/l at 08.00 hours (p〈0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng·min· ml−1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r=0.87, p〈0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r=−0.48, p〉0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.
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  • 7
    ISSN: 1434-9949
    Keywords: Ankulosing spondylitis ; Microradiography ; Tetracycline labelling ; Calcified elastin ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five spine specimens obtained at autopsy and five biopsies of sacroiliac joints from subjects with ankylosing spondylitis were submitted to microradiography and to fluorescence microscopy for detection of tetracycline. Decalcified histological sections were also prepared. Microradiography provides a link between the clinical X-ray picture and the classical decalcified section; it enables calcified cartilage, and hence the early stage of most syndesmophytes to be recognised more easily and accurately; It revealed a peculiar calcification of elastic fibers of the ligamentum flavum. Tetracycline labels showed that: in an early case of sacro-iliac arthritis, calcification of the articular cartilage might partly explain the desification of the X-ray picture; syndesmophytes were thickening at both their superficial and deep faces; thickening, lengthening and internal remodelling of the intervertebral bridges occured together; and calcium was deposited at the end-plates as well.
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 335 (1988), S. 410-414 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A network of cosmic strings generated in the early Universe may still exist today. As the strings move across the sky, they produce, by gravitational lensing, a characteristic pattern of anisotropies in the temperature of the cosmic microwave background. The observed absence of such ...
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  • 9
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
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  • 10
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Mutants of E. coli specifically deficient for the enzyme altronic hydrolyase have been isolated. These strains are unable to metabolize galacturonate but still normally grow on glucuronate; inducibility for the other galacturonate-induced enzymes is not modified. The position of these mutations called “uxaA” locus in relation to the argG, tolC and metC markers was established both by sexual crosses and by P1 transduction; evidence is presented that uxaA is located between argG and tolC. Biochemical characterization of uxaA mutants using thermosensible revertants or mutants was achieved by means of thermal inactivation and kinetic parameters determination. Experimental results strongly suggest that uxaA locus is the structural gene of the altronic hydrolyase enzyme.
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