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Biomedical subjects

H P Schwarz

Publications and source records attributed to H P Schwarz.

At least 19 recordsLinked to original sources
PubMed2006

Young adults born small for gestational age: is reduced baroreceptor sensitivity a risk factor for hypertension?

UNLABELLED: BACKGROUND. Adults born small for gestational age (SGA) are at increased risk for the metabolic syndrome and cardiovascular disease. HYPOTHESIS: Impaired short-term blood pressure regulation may contribute to the development of hypertension in patients born SGA. METHODS: In all, 43 patients born SGA (18 female, age 19.4 +/- 0.3 years) were evaluated by beat-to-beat blood pressure and heart rate registration during rest and mental and orthostatic stress. The study group was divided into Group 1 with normal resting blood pressure (n=32) and Group 2 with slightly elevated blood pressure (n=11). Baroreceptor sensitivity (BRS) was calculated. Fasting insulin as well as lipid levels were correlated with hemodynamic parameters. RESULTS: Eleven of the 43 study patients (25%) had a slightly elevated resting systolic blood pressure (SBP) rising during mental and orthostatic stress. Body mass index (BMI) and fasting insulin levels correlated strongly with SBP in Group 2. Baroreceptor sensitivity was lower in Group 2 at rest (p < 0.05). CONCLUSIONS: Three components of metabolic syndrome (elevated BP, high BMI, elevated insulin levels) correlate strongly in young adolescents born SGA; BRS is reduced in prehypertensive patients. Close follow-up is warranted during adult life as they are predisposed for developing a metabolic syndrome with elevated cardiovascular risk.

Female↗
PubMed2006

Fc function of a new intravenous immunoglobulin product: IGIV 10% triple virally inactivated solution.

BACKGROUND AND OBJECTIVES: Baxter AG has developed a new liquid intravenous immunoglobulin product [Immune Globulin Intravenous (IGIV) 10%] using a new manufacturing procedure. A modified Cohn fractionation and ion exchange chromatography is used to produce an IgG solution with no alterations to the Fc region. Three dedicated virus reduction steps are included: solvent-detergent treatment, nanofiltration, and incubation at low pH and elevated temperature in final formulation. We applied the reference method of the European Pharmacopoeia (EP) together with a flow-cytometric binding assay for the evaluation of the Fc function of the new product. MATERIALS AND METHODS: The EP reference method was done as described in the EP. The flow-cytometric method measured binding of IgG to Fc receptors of human monocytic THP-1 cells after exclusion of apoptotic cells. RESULTS: Sixteen lots of the new product expressed Fc functions between 84% and 110% when analysed with the EP reference method and Fc-binding activities between 82% and 121% when determined by the flow-cytometric method. CONCLUSION: All tested lots of the new product demonstrated a high level of Fc activity and met the requirements of the EP for Fc function.

Flow Cytometry↗
PubMed2006

Pubertal height gain in Ullrich-Turner syndrome.

Short stature and ovarian failure are the main features in Ullrich-Turner syndrome (UTS). The aim of this retrospective analysis was to evaluate the influence of age at initiation of puberty on final height. Sixty-five girls were treated with growth hormone (GH) and had a final height of 150.6 +/- 5.7 cm; 12/65 entered puberty spontaneously. A non-GH treated group of 12 girls with UTS reached a final height of 147.3 +/- 6.6 cm. Subdividing the GH treated group (n = 53) based on the age at induction of puberty, before or after 13 years, there was no significant difference in final height. Final height was affected by the age at which GH treatment was initiated, height SDS at the beginning of puberty, and by the duration of GH therapy. Therefore, early treatment with GH for short stature in UTS should be attempted so that an age adequate initiation of puberty will be feasible.

Adolescent↗
PubMed2005

Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography.

Osteopenia and growth retardation have been described in children with chronic arthritis. GH has an impact on both. In the present controlled study, we used peripheral quantitative computed tomography to evaluate forearm bone mass, density, and geometry as well as forearm muscle and fat area in 17 patients with juvenile idiopathic arthritis (JIA) receiving treatment with GH for 3.8 +/- 1.1 yr compared with an untreated age- and sex-matched control group (n = 17). All patients had a mean age of 15.3 +/- 2.5 yr and a mean duration of illness of 8.2 +/- 4.4 yr. Height, weight, body mass index, bone parameters, and muscle area were significantly decreased in both groups compared with those in healthy age-matched children. Compared with untreated JIA patients, GH-treated JIA patients had significant higher bone mineral content as well as total cross-sectional area (CSA), cortical CSA, and muscle CSA. Fat CSA was lower in the GH-treated group. A significant difference between groups for height-corrected cortical and muscle areas was only seen in male patients. Cortical CSA relative to muscle CSA was not different between groups. These findings are compatible with an anabolic effect of GH on muscle and bone development.

Adolescent↗
PubMed2005

Immunomodulatory properties of human serum immunoglobulin A: anti-inflammatory and pro-inflammatory activities in human monocytes and peripheral blood mononuclear cells.

Our study investigated the immunomodulatory activities of human plasma-derived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro- or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide (LPS, endotoxin)-stimulated human adherent monocytes and human peripheral blood mononuclear cells (PBMC). Our results indicate that IgA down-modulates the release of the pro-inflammatory chemokines monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1alpha and MIP1beta from LPS-stimulated PBMC and the release of MCP1, MIP1alpha and MIP1beta from LPS-stimulated monocytes. Furthermore, we confirmed previous reports that plasma-derived serum IgA down-modulates the release of the pro-inflammatory cytokines, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, from LPS-stimulated monocytes and PBMC, and up-regulates the release of IL-1 receptor antagonist (IL-1RA) from resting and LPS-stimulated monocytes and resting PBMC. This IgA-mediated up-regulation of IL-1RA is independent of the simultaneous up-regulation of IL-1beta release, as shown by blocking the biological activity of IL-1beta with a neutralizing antibody. On the other hand, we also found an IgA-induced pro-inflammatory activity, namely IgA-mediated up-regulation of the release of pro-inflammatory IL-1beta as well as down-regulation of the anti-inflammatory cytokines IL-10 and IL-12p40 from LPS-stimulated monocytes and PBMC and a down-regulation of transforming growth factor (TGF)-beta from resting and LPS-stimulated PBMC. We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.

Cells, Cultured↗
PubMed2004

Musculoskeletal and functional muscle-bone analysis in children with rheumatic disease using peripheral quantitative computed tomography.

Bone demineralization is a severe complication of juvenile idiopathic arthritis (JIA) and other rheumatic diseases. To identify patients, who are at risk of bone disease, musculoskeletal analysis is performed. Furthermore, a more functional approach is needed to assess, whether bone strength is adequate for muscle force and whether muscle force is adequate for body size. In patients with a chronic disease it is most important to differentiate between primary bone problems and those that are secondary to low muscle force. To implement this approach, we measured musculoskeletal parameters of the radius in 94 patients with juvenile idiopathic arthritis of different subtypes and connective tissue disease using peripheral quantitative computed tomography. The four groups consisted of patients with oligoarticular (n = 31), polyarticular (n = 27), systemic JIA (n = 20) and connective tissue disease (CTD) (n = 16). All patients with systemic JIA and CTD and 56% of the patients with polyarticular JIA were under treatment with glucocorticoids. In general, the longer the duration of the disease and the more severe the subtype of the rheumatic disease, the shorter the height and the lower the bone density and bone strength parameters. Mean height, bone mineral content (BMC) and muscle cross-sectional area (CSA) were low for age, but muscle CSA was normal for height with the exception of patients with polyarticular disease. In the systemic JIA group the ratio of BMC per muscle CSA was decreased by -1.7+/-2.7 SD (P < 0.05), suggesting that bone strength was not adequately adapted to muscle force. This was even more expressed in females than in males (14 versus 3). These patients need closer follow up and potential specific therapeutic intervention.

Adolescent↗
PubMed2004

FEIBA: mode of action.

FEIBA (factor eight inhibitor bypassing activity) has a history of more than 30 years of successful use in controlling bleeding in haemophilic patients who have developed inhibitory antibodies against factor (F)VIII or FIX. Recently it was shown that FEIBA contains the proenzymes of the prothrombin complex factors, prothrombin, FVII, FIX and FX, but only very small amounts of their activation products, with the exception of FVIIa, which is contained in FEIBA in greater amounts. FEIBA controls bleeding by induction and facilitation of thrombin generation, a process for which FV is crucial. A number of biochemical in vitro and in vivo studies have shown that FXa and prothrombin play a critical role in the activity of FEIBA. Consequently, they are considered to be key components of this product. The prothrombinase complex has been found to be a major target site for FEIBA. Apart from prothrombin and FXa, FEIBA contains other proteins of the prothrombin complex, which could also facilitate haemostasis in haemophilia patients with inhibitors.

Animals↗
PubMed2004

Thrombin generation assay and other universal tests for monitoring haemophilia therapy.

Factor VIII bypassing agents have different multiple modes of action, but share the common feature of inducing or facilitating thrombin generation. The information obtained from most overall assays to measure the haemostatic response to inhibitor-bypassing agents is limited to the initial phase of blood coagulation (clotting time measurement) or the formation of a solidifying clot followed by fibrinolysis (thrombelastography), and excludes the real endpoint of thrombin generation. Thrombin generation assays (TGAs) measure the whole kinetics of thrombin generation even after the clot formation, and thus assess all activating and inactivating systems of coagulation. Therefore, TGAs are not only becoming a universal tool to improve understanding of haemostasis and to investigate biochemical principles of the haemostatic system, but are also evolving as a powerful prognostic and monitoring tool for inhibitor bypassing therapies.

Blood Coagulation Factors↗
PubMed2003

Monitoring the bioavailability of FEIBA with a thrombin generation assay.

BACKGROUND: Hemophilia A patients with inhibitors are generally treated with preparations containing activated coagulation factors to achieve hemostasis by bypassing factor (F)VIII. OBJECTIVES: We developed an assay for monitoring the kinetic of thrombin generation in human FVIII inhibitor plasma reconstituted in vitro with activated prothrombin complex concentrate, FEIBA, and in plasma samples from hemophilia A patients taken after FEIBA treatment. PATIENTS AND METHODS: For pharmacokinetic studies three patients with severe hemophilia A and with a high-titer inhibitor received a single dose of FEIBA. Repeated FEIBA treatment was monitored in one patient with acquired hemophilia A. Coagulation was triggered in citrated plasma by adding a low concentration of tissue factor/phospholipid complex and CaCl2 in the presence of a fluorogenic thrombin substrate. The intensity of the fluorescence signal (FU) was continuously monitored, and the rate of increase in the fluorescence signal for every time point, which reflects the actual thrombin concentrations, was calculated. RESULTS: The maximum rate of substrate conversion, which indicates the highest thrombin concentration, was approximately 1900 FU min(-1) in a normal plasma pool. Practically no thrombin generation was observed in the FVIII inhibitor plasma, but when it was spiked with FEIBA, the rate and the peak of thrombin generation increased dose-dependently to close to normal. Plasma samples from FVIII inhibitor patients treated with a single dose of FEIBA had an improved thrombin maximum within an hour after treatment, which gradually returned to baseline values with a half-life of 4-7 h. Changes in the characteristic parameters of thrombin generation coincided with the repeated administration of FEIBA in a patient with acquired hemophilia A. CONCLUSIONS: This assay enables the pharmacodynamic and pharmacokinetic properties of bypassing therapies to be monitored, thus helping to optimize treatment.

Adult↗
PubMed2003

Growth hormone improves height in patients with juvenile idiopathic arthritis: 4-year data of a controlled study.

OBJECTIVE: To evaluate the efficacy and safety of growth hormone treatment in severely growth retarded children with juvenile idiopathic arthritis (JIA) receiving glucocorticoids. STUDY DESIGN: Children with systemic and polyarticular idiopathic arthritis (22 F, 16 M) with a mean age of 10.1 years were enrolled in this controlled study. Eighteen patients (9 F, 9M; mean age, 10.5 years) received growth hormone in a dose of 0.20 to 0.33 mg/kg body weight per week for 4 years. Twenty patients (13 F, 7 M; mean age, 9.6 years) served as an untreated control group. RESULTS: Mean improvement in height in the treated group was 1 SD, whereas the patients of the control group lost 0.7 SD. Disease activity markers correlated significantly with the mean growth velocity standard deviation score. In general, children with mild or moderate disease and lower comedication grew and responded better to growth hormone therapy than those with active disease. No adverse events were noted. CONCLUSION: Our data suggest that long-term growth hormone therapy has a beneficial effect in children with severe forms of JIA. Further data are needed to confirm the efficacy and safety of growth hormone and its effect on final height.

Arthritis, Juvenile↗
PubMed2003

Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay.

Factor VIII (FVIII)-bypassing agents have complex modes of action but all control bleeding in inhibitor patients by triggering the generation of thrombin. No routine test is available for monitoring this therapy in patients with inhibitors against FVIII. We present an assay that records FEIBA- or FVIIa-mediated changes in thrombin generation (TG) in FVIII inhibitor plasma samples. In plasma samples spiked with FEIBA TG was normalized above 0.4 U/ml, while for recombinant FVIIa (rFVIIa) more than 12.5 microg/ml were required to induce TG in the absence of tissue factor (TF). Addition of TF increased the TG potential of rFVIIa in vitro. This assay seems suitable for monitoring the pharmacokinetics of inhibitor bypassing agents during treatment and possibly for predicting responses to treatment.

Autoantibodies↗
PubMed2002

Weight in adolescents with type 1 diabetes mellitus during continuous subcutaneous insulin infusion (CSII) therapy.

Continuous subcutaneous insulin infusion (CSII) has become increasingly popular as a form of intensified insulin therapy in adolescents with type 1 diabetes mellitus (DM). One reported drawback was increased weight gain in adolescents after initiation of insulin pump therapy. In a prospective, longitudinal, non-randomized and case controlled study, we followed 12 adolescents (mean age 13.6 yr, 8 males, 4 females) from 6 months before the start of CSII to 12 months on CSII. These 12 adolescents with DM on CSII were matched for age, gender, HbA1c, duration of DM, and body mass index (BMI) with 12 adolescents who continued on multiple injection therapy (MIT). In addition, six of the 12 adolescents on CSII intended to control their weight by means of the insulin pump. These six vs six adolescents within the CSII group were further analyzed for weight development and eating habits. Clinical indications for CSII were dawn phenomenon, night-time hypoglycemia and patient request for more flexibility in DM management. All patients had been in satisfactory metabolic control on MIT. After 12 months of CSII, the daily insulin requirement remained significantly lower than 18 months before (0.79 +/- 0.11 vs 1.02 +/- 27 U/kg/d, p = 0.034) and number of daily meals was lower (4.1 +/- 0.9 vs 6.5 +/- 0.7, p = 0.006). Mean initial HbA1c was 7.4% in the MIT and CSII patients, and remained comparable between these two groups. BMI was not different between the CSII and MIT group over the entire study period. However, those adolescents on CSII who intended to control their weight by means of the insulin pump were able to achieve relative weight loss during the,first 6 months on CSII. Two patients of the CSII group had one severe hypoglycemic episode with loss of consciousness. In conclusion, CSII does not lead to weight gain by itself, but allows sufficient weight control without a negative effect on metabolic control. The general threat of weight gain in patients who switch to insulin pump therapy must be pointed out, and the role of eating habits and caloric content of food should play a central role in insulin pump educational programs.

Adolescent↗
PubMed2002

Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001.

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

Adolescent↗
PubMed2001

CYP21 mutations in simple virilizing congenital adrenal hyperplasia.

We studied the functional and structural effects of two unique missense mutations in CYP21 found in patients with simple virilizing congenital adrenal hyperplasia. The rare variants L300F and V281G were found in two girls who were each hemizygous for one of the mutations. Functional analysis after expression in COS-1 cells revealed that the mutant enzymes had reduced enzymatic activity for conversion of both 17-hydroxyprogesterone (L300F 9.5%, V281G 3.9% of normal) and progesterone (L300F 4.4%, V281G 3.9% of normal). Both mutant enzymes had an increased degradation in mammalian COS-1 cells compared to the normal protein, although the L300F variant affected the degradation pattern to a greater extent. Our data indicate that the residue L300 is important in maintaining normal structure of the 21-hydroxylase enzyme whereas mutations affecting V281 most likely cause impaired enzyme activity by interfering with a specific function(s) of the protein.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Mothers with congenital adrenal hyperplasia and their children: outcome of pregnancy, birth and childhood.

OBJECTIVES: Fertility rates in women with congenital adrenal hyperplasia (CAH) are reported to be poor, but few data are available. We assessed rates and course of pregnancy, mode of delivery and long-term outcome of offspring from women with CAH. DESIGN: A large cohort of women with CAH due to 21-hydroxylase deficiency had initially been diagnosed and followed at one centre. Those women who had given birth were contacted. Information was gathered from hospital records, direct patient contact, structured questionnaire and the Documentation of Pregnancy and Preventive Care Booklets. RESULTS: Between 1978 and 1998, 18 women with CAH (one salt wasting, 12 simple virilizing, five nonclassical) had given birth to 31 children (18 females, 13 males). Delivery was by Caesarean section in 16 out of the 31 children. None of the female newborns was masculinized. Twenty-nine children were born at term, five children were small for gestational age (SGA). Postnatal development was basically normal in all children; 18 are now older than 10 years, seven are between 5 and 10 years old, six are less than 5 years old. CONCLUSIONS: Fertility is reduced in females with CAH, especially those with the severe or salt wasting phenotype. In those women with CAH who do conceive, course and outcome of pregnancy is mostly uneventful, although the rate of SGA offspring may be increased. Psychomotor and somatic long-term development of the children was within normal limits.

Adrenal Hyperplasia, Congenital↗
PubMed2001

Preparation and properties of an alpha-1-protease inhibitor concentrate with high specific activity.

BACKGROUND AND OBJECTIVES: Because the current demand for alpha-1-protease inhibitor (A1PI) exceeds the available supply, we aimed to develop a process for purification of A1PI from plasma which would achieve the highest possible degree of purity, specific activity and yield. MATERIALS AND METHODS: A1PI was purified from Cohn fraction IV-1,4 using ethanol precipitation and Q-Sepharose chromatography. Ceramic hydroxyapatite chromatography was used as a final purification step. Two independent virus-inactivation procedures (chemical and vapour heating) were applied. RESULTS: The resulting A1PI had an unprecedented high specific activity. In addition, the process led to the discovery of a new isoform of A1PI in isoelectric focusing gels. CONCLUSION: The high specific activity of the A1PI preparation achieved with this process should allow a reduction of the A1PI total protein load necessary to achieve clinically relevant effects.

Blood Proteins↗