Comparative analysis of organ-specific autoantibodies and celiac disease--associated antibodies in type 1 diabetic patients, their first-degree relatives, and healthy control subjects.

OBJECTIVE: In type 1 diabetes the coexistence with other endocrine diseases and organ-specific autoantibodies has been frequently reported leading to the concept of autoimmune polyendocrine syndrome (APS). In addition, an association of type 1 diabetes with celiac disease has been described. These disorders share a similar genetic background, and first-degree relatives of type 1 diabetic patients may also be affected significantly. Screening for specific antibodies allows early diagnosis of these disorders. RESEARCH DESIGN AND METHODS: In the present cross-sectional study, we analyzed sera from 197 recent-onset type 1 diabetic patients at the time of diagnosis, 882 first-degree relatives, and sera of 150 healthy control subjects for prevalence and co-occurence of the following antibodies (method): insulin autoantibodies (radioimmunoassay); GAD and IA-2 antibodies (radioligand assay); islet cell antibody, anti-adrenal cortex antibodies, and anti-gastric parietal cell antibodies (indirect immunofluorescence); anti-thyroglobulin and anti-thyroid peroxidase antibodies; and gliadin IgG/A and tissue-transglutaminase IgA (enzyme-linked immunosorbent assay). RESULTS: The overall frequency of gastric patietal cell antibodies and adrenal antibodies did not differ significantly among groups. In contrast, type 1 diabetes-associated antibodies and thyroid antibodies were significantly more frequent both in recent-onset type 1 diabetic patients and in the group of first-degree relatives (P < 0.05). The prevalence of gliadin IgG/IgA and transglutaminase IgA was significantly higher in the group of recent-onset type 1 diabetic patients (P < 0.05), but the difference between first-degree relatives and control subjects did not reach statistical significance. Focusing on the coexistence of antibodies, the group of recentonset type 1 diabetic patients presented with 27.4% of the subjects testing antibody-positive-specific for two or more of the envisaged disorders (i.e., type 1 diabetes, autoimmune thyroiditis, and celiac disease) compared with 3.1% in the group of first-degree relatives and 0 of 150 in the control population (P < 0.05). CONCLUSIONS: We conclude that, in an active case-finding strategy, recent-onset type 1 diabetic patients should be routinely screened at least for concomitant autoimmune thyroid disease and additionally for celiac disease. Screening in their first-degree relatives should include at a minimum the search for thyroid autoimmunity in addition to screening for pre-type 1 diabetes.

A rapid quantitative method based on motility of bull sperm cells for in vitro toxicity testing of biomaterials.

A quantitative method for in vitro toxicity testing of biomaterials, based on measurements of time-dependent changes of bull sperm motility, is described. In comparison to the haemolytic and toxic effects of biomaterials such as polyurethanes, poly(vinyl chloride) tubes and bioglass ceramics on erythrocytes and the proliferation rate of human embryonic lung fibroblasts, this method is shown to be more sensitive. The simplicity, rapidity and reproducibility of the test under application of genetically identical cells are advantages that make it suitable for screening large numbers of samples. The quantification of test results allows inter-laboratory comparison.

Ultrasound-guided puncture of the subclavian vein.

The localisation of arteries or veins is facilitated by the use of an ultrasound Doppler unit. This method has proved particularly valuable when dealing with deep lying vessels which are neither visible nor palpable. Until recently, such vessels had to be punctured blindly. This technique employs the Doppler ultrasound-method, which is especially used in the diagnosis of diseases of the peripheral vessels. There also not only useful for the localisation but able to assist the puncture of the vessel.

Scintigraphic monitoring of catheter-port systems in type I diabetics with continuous insulin therapy.

OBJECTIVE: We developed a non-invasive scintigraphic procedure to control the function of percutaneous catheter-port systems for continuous insulin therapy. The aim of the study was to evaluate the scintigraphic results and to compare the absorption kinetics of intraperitoneal and umbilical catheter-ports. MATERIAL AND METHODS: Seven patients with intraperitoneal and nine patients with umbilical catheter-port systems implanted into the partially redilated umbilical vein were investigated. All these patients had normal functioning catheter-ports. Additionally, three patients with intraperitoneal and three patients with umbilical catheter-port dysfunction confirmed either by radiography or laparoscopy were studied. After the injection of (99 m)TcO (4)(-) into the port a region-of-interest was drawn around the activity at the tip of the catheter and the half-life of tracer absorption (T(1/2)) calculated. RESULTS: The normal intraperitoneal catheter-port group showed a T(1/2) value of 6.7 +/- 3.2 min and the normal umbilical catheter-port group a T(1/2) of 6.6 +/- 2.0 min. There was no significant difference in T(1/2) between intraperitoneal and umbilicial systems. The dysfunctional catheter-port group (T(1/2) 19.3 +/- 6.7 min) differed ( p = 0.0005) from the normal catheter-port group (T(1/2) 6.7 +/- 3.2 min). On the basis of the normal group an upper threshold value of T(1/2) was calculated to be 11.8 min. CONCLUSIONS: Imaging with (99 m)TcO (4)(-) is an accurate, non-invasive, and quick method to assess the function of insulin catheter-ports. A T(1/2) value > 11.8 min is indicative of a catheter dysfunction. Umbilical and intraperitoneal catheter-ports show similar absorption rates of (99 m)TcO (4)(-).

Cardiac transplantation in patients with insulin-treated diabetes mellitus.

BACKGROUND AND METHODS: As documented earlier the incidence of cardiac mortality in diabetic patients due to coronary artery disease is high. Cardiac transplantation for congestive heart failure due to coronary artery disease, cardiomyopathy, and valvular diseases is obviously a therapeutic option in patients suffering from insulin-treated diabetes mellitus. To shed more light on this problem we performed a retrospective analysis of 40 patients with insulin-treated diabetes mellitus (three type-1; 37 type-2: insulin-treated for at least three months before cardiac transplantation) referred to our transplant unit for cardiac transplantation between March 1989 and December 1996. RESULTS: Orthotopic cardiac transplantation was performed in 40 patients (4 women, 36 men) aged 32-73 years (mean 56 years) with an insulin-treated diabetes mellitus preexisting for 3-348 months (mean 65.1 months). Donor age ranged from 15 to 72 years (mean 35.5 years) matched for body weight and blood group. Overall mortality in this group was 40.0% with an early mortality of 12.5%. CONCLUSIONS: Our results show that type-1/2 insulin-treated diabetes mellitus preoperative to heart transplantation is not a contraindication in patients suffering from end-stage heart failure. Adequate therapy of diabetes mellitus as well as individual immunosuppressive therapy are important in order to minimize additional organ damage caused by the drugs themselves or resulting infectious complications.

The Giessen-Bad Oeynhausen family study: improved prediction of type I diabetes in a low incidence population of relatives using combinations of islet autoantibodies in a dual step model.

To determine the value of a combined antibody screening for prediction of type I diabetes in a low incidence cohort, we prospectively studied 882 first-degree relatives (485 parents, 382 siblings and 15 offsprings) for up to 11 years who were not preselected for islet cell antibody (ICA) status. During the observation period, 16 individuals developed diabetes. The first serum sample obtained at study entry was analyzed for ICA and antibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and anti-IA-2ic. A multivariate analysis, according to the Cox proportional hazard model considering the joint effects of all baseline variables, selected the four antibodies and the specific family history as significant risk confounding factors (p < 0.05). Further analysis by Kaplan-Meier Life-table methods confirmed a significantly increasing risk of diabetes with the number of autoantibodies present (p < 0.001). In accordance with the Cox model, relatives with more than one affected family member (a multiplex pedigree) and siblings and offsprings vs. parents were at increased risk of IDDM (p < 0.05). In addition to technical problems, a screening strategy based on initial ICA testing has the potential of missing ICA negative subjects among future cases of type I diabetes (19% were ICA negative in the present study) and we therefore set out to evaluate an alternative approach using a dual step strategy with a combination of GADA and anti-IA-2ic for initial screening followed by retesting of positive individuals for ICA and IAA. The combination of GADA and anti-IA-2ic for primary screening (step 1) proved to be more sensitive, identifying 94% of future cases of type I diabetes compared to 81% using ICA as initial test and this antibody combination identified 93% of those individuals with ICA of 20 JDF or more. Retesting of positive individuals for ICA and IAA (step 2) significantly improved the positive predictive value confering a risk of diabetes for siblings and offsprings with more than 2 antibodies within 5 years of 67% (95%CI: 39-90). We conclude that the prognosis of contracting IDDM in relatives is strongly related to the number of autoantibodies present, but the family history should be additionally considered for individual risk assessment. The proposed screening strategy could overcome the inherent problems of the ICA and IAA assays for large-scale screening. In the present study it allows 5-year risk estimates of up to 67% identifying 94% of future cases of type I diabetes.

Coping with employment discrimination against diabetics: trends in social medicine and social psychology.

In many European countries, social-medical aspects in the management of diabetes mellitus are not satisfactorily respected. Our contribution reports a study addressing the impact of diabetes on the patient's career and daily work, in order to determine the extent to which diabetics are being discriminated against at work. Type I diabetics were questioned about their experience, and not on the objective burden. A questionnaire was developed to evaluate patients' social and employment problems. Few elements of an education program for Type I diabetes optimizing social skills (social competence) are demonstrated. In a group of 6-8 patients, assertive behavior in the work place is modelled (e.g., for hypoglycaemia, social phobia) by applying psychological methods (behavior modification role-playing). These methods can help diabetic patients to master their discrimination. They learn assertive behavior in social situations with superiors and colleagues and develop self-confidence (self-efficacy). This special education program supports Type I diabetics in coping with employment discrimination.

Effect of time of insemination relative to ovulation on fertility with liquid and frozen boar semen.

Precise data on fertility results following peri- and postovulatory insemination in spontaneously ovulating gilts is lacking. Using transcutaneous sonography every 4 h during estrus as a tool for diagnosis of ovulation, the effects of different time intervals of insemination relative to ovulation were investigated with liquid semen (Experiment 1, n=76 gilts) and frozen semen (Experiment 2, n=80 gilts). In Experiment 3 (n=24 gilts) the number of Day-28 embryos related to the various intervals between insemination and ovulation was determined after the use of liquid semen. Using liquid semen the fertilization rates based on Day-2 to Day-5 embryos and the number of accessory spermatozoa decreased significantly in gilts inseminated with 2 x 10(9) spermatozoa per dosage in intervals of more than 12 h before or more than 4 h after ovulation. In the time interval 4 to 0 h before ovulation, comparable fertilization rates were obtained using frozen semen (88.1%) and liquid semen (92.5%). Fertilization rates and numbers of accessory spermatozoa decreased significantly when gilts were inseminated with frozen semen more than 4 h before or 0 to 4 h after the detection of ovulation. The percentage of Day-28 embryos was significantly higher following preovulatory insemination compared to inseminations 0 to 4 h and 4 to 8 h after ovulation. It is concluded that the optimal time of insemination using liquid semen is 12 to 0 h before ovulation, and 4 to 0 h before ovulation using frozen semen. The results stress the importance of further research on sperm transport and ovulation stimulating mechanisms, as well as studies on the time of ovulation relative to estrus-weaning intervals and estrus duration.

The initial fertilizing capacity of longerm-stored liquid boar semen following pre- and postovulatory insemination.

In pigs, high variation is seen in the duration of estrus and in the time of ovulation. This is one of a wide range of factors not related to semen quality, which possibly influences the results of field insemination trials. Experiment 1 (n=81 gilts) was performed to determine the influence of the time of ovulation on the fertilizing capacity of liquid boar semen stored up to 118 h. The objective of Experiment 2 (n=102 gilts) was to study the fertilizing potential of semen stored up to 120 h in 2 different extenders, Androhep and Beltsville Thawing Solution (BTS), by means of postovulatory AI. Inseminations were performed 0 to 4 h after ovulation in order to standardize the trial conditions. Fertilization rates based on Day-2 to Day-4 embryos, and the number of accessory spermatozoa per zona pellucida did not differ between semen stored for 0 to 48 and 48 to 87 h in gilts ovulating within 12 after insemination (Experiment 1). Gilts with an interval of 12 to 24 h between AI and ovulation had lower fertility results using semen stored for more than 48 h. A further decrease was observed when semen storage exceeded 87 h in those gilts ovulating later than 24 h after insemination. The time of ovulation has to be considered as being a major factor of variation in the fertility results of AI trials. In Experiment 2, fertilization rates and numbers of accessory spermatozoa decreased between semen stored for 0 to 24 and 24 to 48 h in BTS, and between semen stored for 0 to 24 and 48 to 72 h in Androhep. Significant differences in fertility between diluents were seen only when using semen stored for more than 96 h, with semen extended with Androhep giving the higher results. The results indicate that the decrease in fertilizing capacity due to in vitro aging of spermatozoa cannot be prevented even during the first days of storage.

Possibilities and limitations of ultrasonic diagnosis of space occupying lesions in internal medicine.

Possibilities and limitations of ultrasonic tumour diagnosis in internal medicine (thyroid gland, liver, pancreas, kidney, malignant lymphomas) are discussed on the basis of a five years experience with about 4,000 examinations a year. A real time and gray-scale technique is used. The accuracy of the presented ultrasonic findings is proven by comparative studies. Besides the well known advantages of ultrasonography the independence from contrast medias must be stressed in comparison to diagnostic radiology. The main limitations of ultrasonography are the impossibility of diagnosing tumours smaller than 1.5-2 cm and the absence of an ultrasonic pattern typical of malignancy. To establish a morphobiological diagnosis, ultrasonically guided fine needle biopsy has proved to be a reliable method.

[Cost reduction in drug therapy of diabetes]. / Kostensenkung bei der medikamentösen Diabetestherapie.

The costs of control an therapy of diabetes mellitus are very expensive. A cost reduction is to be expected after successful therapy. For 1024 insulin dependent type I-diabetics with stable insulin requirements the mean costs remained unchanged. 456 insulin dependent type II-diabetics who reduced weight showed a slight reduction of mean costs. The cost of drug therapy were significantly reduced for 535 overweight type II-diabetics under different therapeutic modalities, who reached a weight reduction. The inpatient treatment of diabetes influences the costs of drug therapy. A cost reduction is to be expected for overweight type II-diabetics, who can reach a weight reduction.