Case management: a method of addressing subject selection and recruitment issues.
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Biomedical subjects
Publications and source records attributed to C Hansen.
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A survey and critical evaluation of the present-day supply of fortified common food products on the German market is presented concerning products, nutrients and amounts for fortification. The data were collected from the original food labels by personal informations from the manufacturers (40 asked, 68% answered) and by a local market survey in Dortmund (spring 1994). A total of 288 fortified food products (78 manufacturers) were found out of 6 different food products (78 manufacturers) were found out of 6 different food categories (manufacturers/products): beverages (26/95), sweets (24/57), cereals (5/53), milk products (7/35), powdered instant beverages (10/31), ready-to-eat meals (6/17). Sugar was added to 56% of the fortified products. A total of 10 vitamins (E, B1, B2, B6, B12, C, niacin, folate, biotin, pantothenic acid) and 7 minerals (Na, K, Cl, Ca, P, Mg, Fe) were used for fortification. The number of nutrients used for fortification in single products ranged from 1 (94 products) to 16 (3 products). The amounts used for fortification per average portion varied considerably among the different products and the different nutrients in the food categories. In a considerable number of cases, amounts for fortification of more than 100% (maximum 660%) of the recommended daily dose of a nutrient (EC-directive for nutrition labelling) have been observed. Relatively to the contribution of a portion to meet the energy requirement, the fortification of cereals and milk-products (about 30%) as well as of sweets (about 10%) could be rated as acceptable whereas the fortification of beverages (about 50-100%) was overdone. The present-day supply of fortified food is extremely heterogenous from the qualitative and quantitative point of view. Therefore, it is rather difficult for the consumer to reach an overall nutrient intake that is in accordance with the recommendations. The specific requirements of children, who are a preferred group for food advertising, are not at all considered adequately.
The roles of reimbursement and other predictors that affect physicians' willingness to accept publicly insured continuing care patients were examined in a national survey. The response rate was 47%. Eighty-eight percent of the respondents were accepting new patients. Forty-two percent of these physicians were willing to accept new continuing care patients insured by Medicaid, 70% reported accepting those paying by Medicare assignment, and 85% said they accept patients covered by Medicare plus balance-billing payments. Low reimbursement was the strongest predictor for lack of acceptance. The results suggest that systems of multitiered reimbursement are associated with diminished access for patients insured in the lower tiers.
The combination of analytical techniques such as PNA and SIMS with a compartmental approach enables the study of the metabolism and biokinetics in humans of several elements by using stable isotopes as tracers. The techniques developed for Te require the administration of greater masses than those used for similar studies performed with radioactive tracers, therefore a test was carried out in rabbits in order to assess the possible influence of the administered amounts on the determination of the biokinetic parameters. The behaviour of the tracers was found to be similar for Te administration of up to 70 micrograms/kg of body weight. An inter-individual variability in the size of the transfer compartment was observed and has to be taken into account.
Endocrine Ophthalmopathy (EO) is based on autoimmune processes that lead to lymphocyte infiltration of the retrobulbar space. In this study, antigenic character of retrobulbar adipose, connective and muscle tissue as well as of cultured fibroblasts and myoblasts were examined. Samples were obtained from EO patients (n = 13, 8 fem., age 26-82 years, median 47 years) undergoing orbital decompression surgery. Retrobulbar and abdominal tissue from 7 controls (4 fem., 48 - 74 y) was investigated, too. Tissues were homogenized and the proteins were separated by SDS-PAGE according to molecular weight. In order to recover the separated proteins in soluble form, an electroelution technique was employed. Twenty-two separated soluble protein fractions were used as antigenic stimuli for autologous peripheral blood mononuclear cells (PBMC) separated by Ficoll gradient centrifugation. Subsequently, the proliferation of T cells was measured by [3H]-thymidine uptake. A marked T cell response to protein fractions with molecular weight of 6 - 10 kD and 19 - 26 kD was detected (p < 0.001). These autoantigens were found readily reproducible in adipose tissue in 8 out of 9 EO patients, stimulation index (SI) to antigen 6 - 10 kD 29 +/- 4.6 (mean +/- SEM); 19 - 26 kD 5 +/- 1.4 and in 3 out of 4 patients using retrobulbar eye muscle tissue (SI: 6 - 10 kD 23 +/- 4.2; 19 - 26 kD 6 +/- 2). Using the proteins of cultured fibroblasts as antigen, the autologous PBMC from 2 out of 4 tested EO-patients also responded (SI: 7 +/- 2; 4 +/- 1.4). Testing cultured retrobulbar myoblasts of an EO patient, a response to the 19 - 26 kD antigen was found only (SI: 8.0). In response to retrobulbar or muscle proteins, PBMC of 2 controls showed also a higher proliferation rate (SI: 16 +/- 3.5; 13 +/- 2.8), whereas, a response to abdominal adipose or muscle proteins (4 controls) was never found. Thus, two orbital antigens reacting with autologous T cells could be demonstrated and may play an important role in the immunopathogenesis of EO. According to these findings, retrobulbar fibroblast antigens are most likely the main T cell targets.
The influence of diabetic nephropathy on urinary glycosaminoglycan distribution was assessed in 96 patients with insulin-dependent diabetes mellitus (IDDM, 49 female, age: 16 - 64 yrs, median 35; duration of IDDM: 0 - 43 yrs, median 13 yrs) in comparison to 103 healthy controls (57 female, 17 - 82 yrs, median 40 yrs). Glycosaminoglycan concentration of 24 h urine samples was determined by means of precipitation with cethylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (p = 0.0008) in urinary glycosaminoglycan excretion between patients (19.0, 12.4, 35.6 mg/24 h, median, 25th, 75th percentile) and controls (15.8, 10.4, 21.6 mg/24h) could be detected. In patients with insulin-dependent diabetes mellitus of longer duration, glycosaminoglycan excretion was increased (<10 years: 17.3, 10.8, 30.5 mg/24 h; > 10 yrs: 23.3, 16.0, 39.1 mg/24 h; p = 0.03). Furthermore, diabetic patients with manifest nephropathy and retinopathy exhibited a significantly higher glycosaminoglycan excretion compared to patients without nephropathy (40.8, 23.3, 42.2 versus 18.2, 11.4, 31.0 mg/24 h, p = 0.005) or retinopathy (31.9, 16.6, 41.6 versus 17.6, 11.2, 26.7 mg/24 h, p = 0.009). Thus, the results of this study demonstrate a close relationship between diabetic nephropathy and the renal glycosaminoglycan excretion.
Molybdenum is a trace element essential to life. Nevertheless, little information is available on its metabolism in humans. A methodology based on stable isotope administration that combines compartmental analysis, simultaneous use of two tracers, and proton nuclear activation (PNA) is presented. A four-compartment metabolic model was adopted. The compartments are stomach, small intestine, transfer compartment, and unquantified tissue pool. The employment of two different stable isotopes of the element under investigation as tracers was made possible by PNA. Optimization of the technique for molybdenum determination in plasma led to the choice of 95Mo and 96Mo as tracers. Their concentrations in plasma can be determined measuring the disintegration gamma lines of the corresponding technetium radioisotopes produced via (p,n) reaction. In the adopted experimental conditions, a minimum detectable concentration of 2 ng isotope/ml plasma was attained. A kinetics study was performed on two healthy volunteers. To both subjects one tracer was orally administered, and the other intravenously injected. Venous blood samples were withdrawn at different postinjection times and the concentrations for both isotopes determined. The model parameters describing molybdenum kinetics were obtained for the two individuals. Total absorbed fraction was found to be 0.84 +/- 0.03 and 0.86 +/- 0.07, respectively.
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The benefit of thrombolytic therapy given late after the onset of acute myocardial infarction (AMI) has been controversial because of low reperfusion rates and limited myocardial salvage. Persistent chest pain has been used as a criteria for late intervention, but there is little documentation to validate this practice. Clinical outcomes and myocardial salvage were evaluated in 74 patients with AMI and persistent chest pain who underwent late reperfusion (> 6 hours) with direct coronary angioplasty, and these were compared with outcomes in 460 patients with early reperfusion (< or = 6 hours). Patients with late reperfusion had a high infarct artery patency rate (96%), a low hospital mortality rate (5.4%), and a low incidence of reinfarction (1.4%) and recurrent ischemia that were similar to patients with early reperfusion. Patients with late reperfusion had surprisingly good recovery of left ventricular function with improvement in ejection fraction from 50% to 60% at follow-up angiography. Patients with late reperfusion had a greater incidence of collateral flow (45% vs 22%, p < 0.001) and a lower value of peak creatine kinase (1,357 vs 2,057 U/liter, p < 0.001) than patients with early reperfusion. This study emphasizes the importance of persistent chest pain as a marker of continued myocardial viability in patients who present late after AMI. These data suggest that the probable mechanism of continued viability is preserved flow to the infarct zone. Patients with AMI and persistent chest pain may benefit from reperfusion therapy beyond 6 to 12 hours.
A method to generate a population of motile, acrosome-reacted mouse sperm is described. Sperm retrieved from the cauda epididymis and vas deferens were first capacitated in a 3% bovine serum albumin (BSA) containing medium. Sperm were then resuspended in medium with low BSA content (0.01%) and treated with 30 nM of the calcium ionophore, A23187, which was added as a single dose of 30 nM for 15 min at 37 degrees C; or three sequential 10 nM doses over three 5 min intervals. Approximately 55-60% of the treated sperm population became acrosome reacted. The motility of the treated sperm sample was 40-65%, slightly lower than that of the control sperm, following addition of medium containing 3% BSA. This is in contrast to the < 10% motility observed for capacitated mouse sperm treated with 10 microM 23187, a concentration that had been used by other investigators to induce the acrosome reaction. The ultrastructure of the 30 nM A23187-induced acrosome-reacted sperm was similar to that of the acrosome-reacted sperm induced by solubilized zonae pellucidae. These motile, acrosome-reacted sperm were able to penetrate zona-free mouse eggs at a higher rate than the control sperm. Thus this method of treatment will be useful for further physiological experimentation with acrosome-reacted sperm.
An increase of retrobulbar adipose tissue has been shown by imaging techniques in patients with Graves' ophthalmopathy (GO). Immunohistochemical staining was applied to investigate the involvement of different retrobulbar (especially adipose) tissue components in the autoimmune process of the disease. Cryostat sections from retrobulbar tissues of 15 GO patients and 11 controls were analyzed with a battery of monoclonal antibodies against CD2, CD4, CD8, CD11a, CD19/22, CD25, CD54, CD57, CD68, C3b, HLA-A, B, C, and HLA-DR. In contrast to controls, the retrobulbar adipose tissue showed an increase of HLA-DR expression, an activation of intercellular adhesion molecule I (ICAM-1, CD54), as well as a marked infiltration of activated T-cells (especially CD4) and macrophages (CD68), whereas a positive staining for interleukin-2 receptors (CD25), T-cells (CD2), B-cells (CD19/22), complement factors (C3b), and LFA-1 (CD11a) was present only in a few patients' specimens. Staining for natural killer cells (CD57) was negative in fat tissue of patients and controls. The perimuscular connective tissue sections of GO patients showed an accumulation of T-cells (CD4/CD8), an enhanced display of ICAM-1, LFA-1, HLA-DR-positive cells, and B-cells. Retrobulbar muscle tissue of GO patients exhibited an increase of CD4, CD8, CD54, CD68, and HLA-DR-positive cells, located in the intramuscular connective tissue, exclusively. In conclusion, the present study underlines the involvement of retrobulbar adipose tissue in the immunopathogenesis of Graves' ophthalmopathy.
With evidence on the important role of glycosaminoglycans (GAG) in the pathogenesis of endocrine ophthalmopathy (EO) having accumulated, the present study focused on the biochemical assessment of plasma GAG content in 37 EO patients as compared to 20 controls. Glycosaminoglycans were isolated from plasma samples by protein elimination, dialysis, and precipitation with ethanol and cetylpyridinium chloride. Patients (9.71, 5.09, 15.09 mg/100 ml; median, 25th, 75th percentile) exhibited significantly (p = 0.0021) higher plasma GAG levels than controls (4.6, 3.38, 6.8 mg/100 ml). Plasma GAG content was unrelated to age, sex, or antithyroid treatment. However, an even higher level of significance (p = 0.0001) was reached when discriminating between untreated patients with EO of recent onset (14.16, 10.35, 15.51 mg/100 ml) and controls. By contrast, steroid therapy of EO led to values (3.82, 1.85, 6.52 mg/100 ml) indistinguishable from those of the controls. Further statistical analysis of the results, based on a specificity of 95% for the control group, revealed a sensitivity of 91% for patients with untreated EO of recent onset, and a specificity of 100% for patients receiving steroid therapy. In comparison, plasma GAG content was determined in 8 untreated and in 6 treated EO patients by a second method already published. All untreated patients exhibited high GAG levels (median 2.23 mg/100 ml) whereas in treated EO patients normal plasma GAG values (0.17-0.34 mg/100 ml) were found. Follow-up determination of plasma GAG content in 7 patients undergoing steroid treatment unveiled a marked decrease of initially elevated values. These findings correlated well with clinical improvement of thyroid eye disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol accounts for 4-6% of the average energy intake in most Western countries. Alcohol-induced hypoglycaemia is a well-known and feared complication in insulin-dependent diabetic subjects, but little attention has been paid to the impact of alcohol on carbohydrate metabolism in non-insulin-dependent diabetes. The aim of the present study was to investigate in non-insulin-dependent diabetic subjects the acute metabolic effects of a moderate amount of alcohol taken with a light meal, conditions chosen to mimic an everyday situation. The patients received 500 ml non-alcoholic beer with an alcohol content (ml/l) of 0 (treatment A) and 54 (treatment B) together with a light meal, implying identity of the contents of ingredients except for alcohol. We found similar serum glucose, insulin, free fatty acid and triacylglycerol responses irrespective of addition of a modern amount of alcohol. In conclusion, a moderate amount of alcohol can be taken with a meal without eliciting hypoglycaemia in non-insulin-dependent diabetic subjects.
In a double-blind, placebo-controlled trial, the effect of 75 mg of a slow-release formulation of amitriptyline on the clinical severity of chronic tension-type headache and on headache-associated neurophysiological parameters (EMG activity, exteroceptive suppression of temporal muscle activity, contingent negative variation (CNV) and experimental pain sensitivity) was investigated. All of the patients treated had a history of headaches of many years standing, and numerous failed attempts at treatment. In the amitriptyline group, a significant reduction in daily headache duration was already found in the third week of treatment, while in the placebo group no significant changes in headache duration were to be seen. In week 6 the amitriptyline group had a significantly shorter daily duration of headache than the placebo group. Treatment did not result in any significant effects on EMG recording of pericranial muscle activity either during relaxation or contraction, on exteroceptive suppression of the temporal muscle and on CNV. The sensitivity to suprathreshold experimental pain, however, was significantly reduced. The data show a statistically relevant reduction of daily headache duration in chronic tension-type headache. However, they also show that amitriptyline can only partly alleviate chronic headaches but cannot cure them.
The effect of thawing velocities ranging from 10 degrees C/min to 1,800 degrees C/min on the motility and acrosomal integrity of boar spermatozoa frozen at 1 degree C/min (suboptimal), 5 degrees C/min, and 30 degrees C/min (optimal) rate was studied with the sperm suspended for freezing in diluent containing 2, 4, or 6% of glycerol (v/v). The influence of thawing on sperm survival depends on the rate at which the sperm had been frozen. In semen frozen at a suboptimal rate of 1 degree C/min, the percentage of motile sperm (FMP) initially fell to 3.5-4.0% when the thawing rose to 200 degrees C/min, but, with further increases in thawing rate, increased and reached peak values (10.3-11.0% FMP) after thawing at 1,800 degrees C/min. The percentage of sperm with normal apical ridge (NAR) also increased moderately with thawing rate, but the degree of improvement decreased as the glycerol level was increased. In semen frozen at 1 degree C/min, acrosomal integrity (NAR) was best maintained in 2% glycerol, reaching 22.9% NAR after thawing at 1,800 degrees C/min. In semen frozen at the optimal rate of 30 degrees C/min, the increases in thawing rates above 200 degrees C/min substantially improved motility. Motility was generally higher in semen protected by 4 or 6% glycerol, with the peak values of 44 or 46% FMP, respectively, after thawing at 1,200 degrees C/min. The proportion of sperm with NAR also increased with thawing rate, but as in the case of suboptimally frozen sperm it was influenced negatively by the glycerol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Restriction fragment length polymorphism (RFLP) analysis, comparative marker chromosome analysis, and polymorphic enzyme analysis was carried out on a total of eight human urothelial cell lines and sublines selected according to our knowledge of their HLA-A,B phenotype. RFLP analysis and cytogenetic analysis showed that the cell lines Hu1703He, Hu1922, and T24 are genuine cell lines of different origin. The identity of Hu1703He could not be confirmed by its isozyme phenotype which was identical to the T24 phenotype. RFLP analysis and isozyme analysis revealed that three cell lines, Hu456, Hu549, and Hu961a, and two transformed sublines, HCV-29Tmv and Hu609Tmv, are sublines of T24. A common origin of Hu456, Hu549, Hu961a, HCV-29Tmv, and Hu609Tmv was confirmed by marker chromosome analysis. However, the T24 origin of these cytogenetically related cell lines was not supported by chromosome analysis of T24. RFLP analysis and HLA phenotyping of two tumorigenic and invasive sublines isolated from a culture of non-tumorigenic Hu609 cells showed that non-tumorigenic Hu609 cells can transform 'spontaneously' in vitro into tumorigenic Hu609T cells. The results emphasise the need for careful monitoring and screening of cell lines for their identity using more than one identification parameter.