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H Schatz

Publications and source records attributed to H Schatz.

At least 37 records · Page 2Linked to original sources
PubMed2003

Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions.

In a general practice observation study 11,476 patients with type 2 diabetes pretreated with oral antidiabetic drugs, mainly metformin, received an oral combination therapy of nateglinide with metformin. Mean age+/-SD of the participants was 61+/-10.3 years, range 19 to 97 years, the body mass index (mean+/-SD) was 29.4+/-4.5 kg/m2, range 14.9 to 68.7 kg/m2. The observation period lasted 3 to 4 months (mean 96 days). During this period the mean HbA1c decreased from 8.4 % to 7.2%, displaying a positive relation between initial value and degree of reduction. Postprandial glucose levels dropped from a mean of 210 to 152 mg/dl. At the beginning of the study the combination of the two target values for glucose control, HbAc <7% and postprandial glucose <180 mg/dl, was reached in only 5.8% of the participants, at the end in 44.9%. During the therapy, weight and blood pressure dropped slightly. Adverse events were reported in only 2.9% of the patients and involved a broad range of symptoms with mild gastrointestinal complaints being predominant (1.3%). This study demonstrated that the combination of nateglinide with metformin can be considered as an effective and safe option for treatment of patients with type 2 diabetes, with additional beneficial effects on body weight and blood pressure.

Adult↗
PubMed2002

Elastic alpha-12C scattering and the 12C(alpha,gamma)16O E2 S factor.

Angular distributions of 12C(alpha,alpha)12C have been measured for E(alpha) = 2.6-8.2 MeV, at angles from 24 to 166, yielding 12 864 data points. R-matrix analysis of the ratios of elastic scattering yields a reduced width amplitude of gamma12 = 0.47 +/- 0.06 MeV(1/2) for the Ex = 6.917 MeV (2+) state in 16O(a = 5.5 fm). The dependence of the chi2 surface on the interaction radius a has been investigated and a deep minimum is found at a = 5.42(+0.16)(-0.27) fm. Using this value of gamma12, radiative alpha capture and 16N beta-delayed alpha-decay data, the S factor is calculated at E(c.m.) = 300 keV to be S(E2)(300) = 53(+13)(-18) keV b for destructive interference between the subthreshold resonance tail and the ground state E2 direct capture.

Journal Article↗
PubMed2002

Circulating transforming growth factor beta1 (TGFbeta1) is elevated by extensive exercise.

Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in immune function, atherosclerosis, fibrotic disease, diabetic complications and bone turnover. It is synthesized in large quantities by bone cells in response to hormones and mechanical stimuli. Plasma contains inactive "latent" TGFbeta1, which consists of the precursor molecule and a TGFbeta1-binding protein. Platelets store latent TGFbeta1 in their alpha-granules, and serum therefore contains large amounts of latent TGFbeta1. We developed a technique for determining latent plasma TGFbeta1 and investigated whether circulating TGFbeta1 is affected by the stimulation of bone formation in response to strength training. Ten healthy students with low training activity participated in a heavy exercise programme over 4 weeks. Blood was drawn into citrate-filled syringes containing prostaglandin E(1) (PGE(1)) and immediately centrifuged at 4 degrees C. TGFbeta1 was determined with a sandwich ELISA standardized with National Institute for Biological Standards and Controls (NIBSC) materials. Six of the ten students completed the training. Highly reproducible values (500-600 pg/ml) of latent TGFbeta1 in plasma were determined. Baseline levels of TGFbeta1 were 525 (50) pg/ml [mean (SE)], which is in the range observed for young adults. TGFbeta1 concentrations rose significantly to 710 (65) pg/ml after 2 weeks of training and thereafter slowly declined to 650 (62) pg/ml after 2 weeks and 440 (33) pg/ml after 4 weeks, respectively. No active TGFbeta1 was detectable in citrate PGE1 plasma samples. Serum levels were between 6000 and 10,000 pg/ml and contained 200-400 pg/ml active TGFbeta1. In contrast to previous reports, plasma did not contain measurable amounts of circulating active TGFbeta1. We demonstrate that heavy exercise transiently elevates latent TGFbeta1 concentrations in plasma. TGFbeta1 is produced by osteoblasts in considerable amounts; therefore, we assume that the observed changes are partly due to enhanced TGFbeta1 production or release in bone, since the quantities of TGFbeta1 produced by other cells are comparably small.

Adult↗
PubMed2002

Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.

The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of neuropathic diabetic foot ulcers, but the knowledge of its impact on the wound healing and healing times in foot ulcers compared to conventional methods of pressure relief is sparse. The aim of this study was to assess the effects on the wound healing of felted foam dressings for plantar pressure reduction in the therapy of neuropathic foot ulcers. This prospective cohort study evaluates healing times and wound healing in 61 diabetic patients with neuropathic foot ulcerations. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study, 27 patients were randomized to the felted foam therapy, and 34 patients were randomized to conventional therapy. In the felted foam group, the initial average wound area was 110.8 +/- 14.4 mm 2 (mean +/- SE), and 2.1 +/- 0.5 mm 2 after ten weeks (p < 0.0001), with an average healing time of 79.6 (95%-CI 75-84) days. In the conventional therapy group, the initial average wound area was 119.2 +/- 13.8 mm 2, and 3.4 +/- 0.7 mm 2 after ten weeks (p < 0.0001). The average healing times was 83.2 (95%-CI 77-90) days. Both with respect to the wound healing process and the healing times, the felted foam technique appears to be as effective as conventional plantar ulcer treatment. We conclude that the felted foam technique is an useful alternative in the therapy of the neuropathic diabetic foot syndrome, especially in patients who are not able to avoid weight-bearing reliably.

Cohort Studies↗
PubMed2001

[Clinical value of urinary pyridinium crosslinks as osteoporosis markers: evaluation of a population survey of vertebral osteoporosis].

BACKGROUND: The diagnostic value of biochemical parameters of bone turnover for the diagnosis of osteoporosis is open to discussion. We investigated whether the determination of crosslinks, bone type I collagen degradation products, correctly identifies osteoporotic subjects. PATIENTS AND METHOD: In a sample of 370 individuals recruited at random within a population survey of vertebral osteoporosis, urinary concentration of total pyridinoline and desoxypyridinoline were determined by HPLC. Standardized lateral X-rays of the thoracic and lumbar spine were taken and evaluated morphometrically using the method described by Eastell-Melton. RESULTS: Crosslink excretion was significantly higher in female but not in male individuals with vertebral deformities as defined by Eastell. The specificity of these biochemical parameters with regard to radiological osteoporotic alterations was 76-81%, but the sensitivity was 32.4-42.9% only. CONCLUSION: Pyridinoline and desoxypyridinoline reflect the process of bone degradation which leads to vertebral deformity. Crosslinks are specific markers of bone resorption and provide a valid parameter in the diagnosis of osteoporosis. The low sensitivity indicates that the measurement of pyridinoline and desoxypyridinoline is less suitable for screening purposes, but may be useful in confirming presence or extent of osteoporosis.

Aged↗
PubMed2001

End point of the rp process on accreting neutron stars.

We calculate the rapid proton ( rp) capture process of hydrogen burning on the surface of an accreting neutron star with an updated reaction network that extends up to Xe, far beyond previous work. In both steady-state nuclear burning appropriate for rapidly accreting neutron stars (such as the magnetic polar caps of accreting x-ray pulsars) and unstable burning of type I x-ray bursts, we find that the rp process ends in a closed SnSbTe cycle. This prevents the synthesis of elements heavier than Te and has important consequences for x-ray burst profiles, the composition of accreting neutron stars, and potentially galactic nucleosynthesis of light p nuclei.

Journal Article↗
PubMed2001

[Assessment of diabetic alterations of microcirculation by means of capillaroscopy and laser-Doppler anemometry].

BACKGROUND: Only minor changes of skin capillary morphology have been described in diabetic patients by means of capillaroscopy, whereas cutaneous microvascular dysfunction is well known. We examined correlations between functional and morphological abnormalities of the capillaries in Type 1 and 2 diabetic patients and the influence of diabetes duration on capillary morphology. PATIENTS AND METHODS: Density, diameters and morphology of nailfold capillaries were investigated in diabetic patients, 16 Type 1 and 19 Type 2, and compared to age- and sex-matched control groups. Capillary blood cell velocities (CBV) during rest and after 3-minute arterial occlusion were measured in the dorsal middle phalangeal area of the left ring finger by means of laser Doppler anemometry. RESULTS: Capillary density, width and arterial limb diameter were similar in Type 1 and 2 diabetic patients compared to their controls. Capillary diameters of the apical part and the venous limb were enlarged in the combined analysis of Type 1 and 2 diabetic patients compared to the control group (apex: 19.2 +/- 0.6 microns vs 17.4 +/- 0.6 microns, p = 0.0243; venous limb: 17.3 +/- 0.5 microns vs 15.9 +/- 0.4 microns, p = 0.0238). Tortuous capillaries were more often observed in Type 1 (n = 13 vs n = 7, p = 0.028) and 2 diabetic patients (n = 16 vs n = 9, p = 0.019) than in controls. In Type 1 diabetic patients an inverse correlation (r = -0.52; p = 0.019) was found between capillary density and resting CBV. In Type 2 diabetic patients capillary apex diameter correlated positively with peak CBV (r = 0.49; p = 0.017). Disease duration correlated inversely with arterial limb diameter (r = -0.48; p = 0.020) and width of the capillaries (r = -0.48; p = 0.018) in Type 2 diabetic patients. CONCLUSION: Tortuous and dilated capillaries, indicating microangiopathy, were found in the skin of diabetic patients by means of capillaroscopy. Using laser Doppler anemometry it is possible to assess impairment of postocclusive reactive hyperemia, due to diabetic microvascular dysfunction, in single capillaries. Correlations between morphological and functional microcirculatory alterations in diabetes may be explained by hemodynamic changes, depending on diabetes duration.

Adult↗
PubMed2001

Anti-MPO-ANCA-positive microscopic polyangiitis following subacute bacterial endocarditis.

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2001

Regulation of protein kinase C by short term hyperglycaemia in human platelets in vivo and in vitro.

AIMS/HYPOTHESIS: Postprandial hyperglycaemia carries an increased risk of macrovascular disease even without Type II (non-insulin-dependent) diabetes mellitus. Chronic hyperglycaemia activates protein kinase C (PKC) in vitro and in vivo but it is not known whether PKC is regulated by short-term post-prandial hyperglycaemia in vivo in humans. We investigated whether PKC is regulated in vivo in hyperglycaemic and hyperinsulinaemic infusion tests and correlated the results to stimulations in vitro. METHODS: Protein kinase C regulation was measured in platelets obtained from 8 healthy subjects who were infused with glucose and insulin for 2 h attaining peak concentrations of 16 mmol/l glucose and in platelets from 8 healthy young subjects, 8 older subjects without diabetes, and 10 older subjects with Type II diabetes after incubation in vitro with 16 mmol/l glucose or glucose and insulin. For precise quantification, a shortened PKC beta1 standard protein was generated by bacterial expression and PKC alpha, beta1, beta2 and delta isoenzyme values were measured by immunoblot analyses. RESULTS: Hyperglycaemic and hyperinsulinaemic in vivo tests increased the amounts of PKC alpha, beta1 and beta2 in the membrane fraction of platelets to 225 +/- 87 %, 164 +/- 22 % and 302 +/- 135 %, respectively, when compared with the baseline values in young healthy volunteers (n = 8, p < 0.05). The expression of PKC delta did not change. In comparison to the recombinant PKC beta1 standard protein, 5 ng PKC beta1/ microg protein was measured before the test and 2 ng/microg were translocated to the membrane fraction after the infusion. No change in the absolute amount of PKC beta1 was detected. In contrast, after incubation in vitro PKC was not regulated by glucose or glucose and insulin in 8 young healthy subjects (age 26 +/- 0.7 years) and in 8 older, healthy subjects (age 64,8 +/- 4 years) although 100 nmol/l 12-O-tetradecanoylphorbol 13-acetate caused maximal activation. In marked contrast, PKC beta1 and PKC beta2, but not PKC alpha or PKC delta, were increased in vitro in the membrane fraction by 292 +/- 61% and 432 +/- 88% (p < 0.05) in 10 subjects with Type II diabetes mellitus matched for age, sex and BMI. CONCLUSION/INTERPRETATION: We found that short-term hyperglycaemia activates PKC alpha, beta1 and beta2 in platelets of healthy persons making them potential candidates for mediating the increased cardiovascular risk of postprandial hyperglycaemia. Hyperglycaemia and hyperinsulinaemia did not cause short-term activation of PKC in platelets in vitro suggesting the existence of additional stimuli. Subjects with Type II diabetes showed a markedly altered reactivity of platelet PKC beta in vitro indicating some diabetes-related regulation.

Adult↗
PubMed2001

Lack of association between antiphospholipid antibodies and thrombocytopenia in patients with Wegener's granulomatosis.

BACKGROUND AND OBJECTIVE: In patients with Wegener's granulomatosis (WG), thrombocytopenia is less common than thrombocytosis. An increased prevalence of antiphospholipid antibodies (aPL), which is associated with thrombocytopenia, has been noted in patients with WG. The aim of this study was to examine the relationship between thrombocytopenia and aPL in patients with WG. METHODS: Thrombocytopenic episodes were searched for in a random sample of 83 patients with WG. Stored sera obtained during thrombocytopenia, which was defined as platelet count below 130 x 10(9)/L, were examined by 2 different enzyme-linked immunosorbent assays (ELISA) for IgG and IgM anticardiolipin antibodies (aCL) and for IgG antiphosphatidylserine antibodies (aPS). Screening for lupus anticoagulant was performed by use of activated partial thromboplastin time (aPTT). Results were compared with the prevalence of aPL in 20 consecutive nonthrombocytopenic patients with WG. RESULTS: Six cases with thrombocytopenic episodes were found in the group of 83 patients with WG. Increased IgG and IgM aCL were detected in 1 patient, who also had elevated IgG aPS. A positive test result solely for IgM aCL was found in another patient. These findings were consistent in both ELISA for aPL. Five patients were being treated with cyclophosphamide when thrombocytopenia occurred. In the group of nonthrombocytopenic patients with WG, elevated IgG aCL and IgG aPS were consistently detected in 1 patient in both ELISA. Three other patients had positive results in single tests, which were not confirmed by the second assay. In all patients, aPTT was normal. CONCLUSIONS: Thrombocytopenia is a rare finding in patients with WG. A similar prevalence of aPL in thrombocytopenic and nonthrombocytopenic patients with WG provides no evidence that aPL play a major role in the pathogenesis of these events. Thrombocytopenia in WG is more likely caused by the myelotoxic effect of preceding cyclophosphamide treatment. We found a frequency of aPL in WG that exceeds frequencies seen in the general population but does not approximate those detected in systemic lupus erythematosus and closely related disorders. Semin Arthritis Rheum 31:4-11.

Adult↗
PubMed2001

Analysis of TGFbeta3 gene expression and protein levels in human bone and serum.

Recent data indicate that TGFbeta3, one member of the TGFbeta-isoforms, has an important role in bone remodeling. Up to date little is known about the expression and regulation of TGFbeta3 in man. We established a highly specific ELISA for quantitative measurement of TGFbeta3 in bone and blood samples and a RT-PCR in combination with HPLC for detection and quantification of TGFbeta3 mRNA in 89 human bone samples. Levels of TGFbeta3 protein ranged between 30 and 66 pg/mg bone (mean 36,6 +/-1,03 pg/mg) and between 30 and 1910 pg/ml in serum (mean 128.9+/-38.9 pg/ml). TGFbeta3 mRNA expression as well as protein levels in serum and in bone declined age dependently. No specific load- or site-specific distribution of TGFbeta3 mRNA expression or protein content was detected at different sites indicating an absence of mechanical regulation. Protein levels of TGFbeta3 in serum correlated with TGFbeta3 mRNA expression in bone (p= 0.0027; r=0.49). By contrast, TGFbeta3 protein levels stored in the bone matrix were not related to TGFbeta3 mRNA reflecting the long term process of TGFbeta3 deposition during bone remodeling. Notably TGFbeta3 serum levels were highly correlated with IGF-I and osteocalcin levels in serum. We conclude that TGFbeta3 in man circulates in significant amounts which appears to be representative for TGFbeta3 expression in bone tissue and may be in part derived from bone. The high correlation of TGFbeta3 with IGF-I suggests parallel systemic principles of regulation.

Adolescent↗
PubMed2001

TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples.

Transforming growth factor beta is one of the most abundant growth factors stored in bone. It is known as a potent regulator of osteoblast proliferation and differentiation as well as of production extracellular matrix. We established a highly specific RT-PCR in combination with HPLC for detection and quantification of TGFbeta1 and TGFbeta2 mRNA expression in 89 human bone samples. Levels of TGFbeta1 protein ranged between 27 and 580 ng/g bone (mean 188 +/- 15 ng/g; n=75) and for TGFbeta2 between 7.2 and 35 ng/g bone (mean 14.3 +/- 2.1 ng/g; n=57). TGFbeta1 and TGFbeta2 protein concentrations and TGFbeta isoform mRNA expression in bone were not significantly different between the sexes. TGFbeta isoform mRNA expression as well as protein content in bone declined age dependently. TGFbeta1 and TGFbeta2 protein and mRNA expression were different in bone samples from different sites of the skeleton indicating in part the regulation by mechanical stimuli. In contrast to TGFbeta1, TGFbeta2 mRNA expression was significantly enhanced in osteoarthritic bone compared to unaffected bone. These data are in concordance to previous results concerning the expression of TGFbeta3 in bone. In conclusion, the data suggest distinct patterns' of expression of the TGFbeta isoforms under physiological and pathological conditions in bone.

Adolescent↗
PubMed2001

Strategies for the prevention of type 2 diabetes.

Type 2 diabetes is a common chronic disease affecting more than 100 millions of people world-wide, and is a major cause of premature morbidity and mortality. Macrovascular disease and its risk factors are often already present in individuals at risk for type 2 diabetes, and some of the risk factors for the development of type 2 diabetes, such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Because some of the metabolic abnormalities, such as insulin resistance or impaired glucose tolerance, that indicate a risk for diabetes can be improved by lifestyle modification and drug treatment, strategies for the prevention of type 2 diabetes appear to be necessary for affected individuals. Several clinical trials have addressed the hypothesis that type 2 diabetes can be prevented by dietary modification, physical activity, or drug treatment. Although some of these studies indicate a protective effect of these measures against the development of type 2 diabetes in people at risk, many of their conclusions are limited with respect to randomisation, sample size, or intensity of the intervention. In the large prospective Da Qing study (1997), both dietary and physical activity interventions reduced the incidence of type 2 diabetes considerably in a Chinese population. Whether this is also achievable in other ethnic populations at high risk for developing type 2 diabetes, and whether additional pharmacological measures are useful, is currently under investigation.

Diabetes Mellitus, Type 2↗
PubMed2001

Modified hyperinsulinaemic, eu- and hypoglycaemic clamp technique using lispro-insulin for insulinoma diagnostic.

SUMMARY: Characterization of metabolically inadequate insulin secretion is essential for insulinoma diagnostics. Hyperinsulinaemic, eu- and hypoglycaemic clamp procedures have been used to suppress endogenous insulin secretion in healthy subjects. The use of exogenous insulin precluded the use of insulin as a parameter to be measured. We now suggest to use exogenous insulin lispro and an insulin-specific ELISA not cross reacting with insulin lispro. Thus, determination of insulin by ELISA in this experimental setting reflects endogenous insulin. A 39-year-old man with a surgically confirmed pancreatic insulinoma was studied under hyperinsulinaemic [lispro insulin 40 mU x m(-2) body surface x min(-1)] clamp conditions. Euglycaemia was achieved (3.8 +/- 0.5 mmol/L) for 1 h and hypoglycaemia (2.36 +/- 0.49 mmol/L) was achieved for another 30 min. Insulin was evaluated by ELISA (cross-reaction with lispro insulin < 0.006%, C-peptide < 0.01%, proinsulin < 0.001%) and by a nonselective RIA (cross-reaction with proinsulin 40%). In control subjects the euglycaemic hyperinsulinaemia suppressed C-peptide to 0.36 +/- 0.03 ng/ml and hypoglycaemic hyperinsulinaemia to 0.29 +/- 0.03 ng/ml. Endogenous insulin was suppressed to 2.8 +/- 0.03 mU/L under euglycaemia and to 2.6 +/- 0.03 mU/L under hypoglycaemia in control subjects. In the insulinoma patient apparently irregular but small changes in both C-peptide (1.43 +/- 0.1 ng/ml) and more pronounced changes in endogenous insulin concentrations 4.41 +/- 0.1 mU/l under euglycaemia and 5.35 +/- 0.3 mU/l under hypoglycaemic conditions, were observed. The basal level of insulin (ELISA insulin 4.6 mU/L) and C-peptide (1.7 ng/ml) were not markedly elevated. Determination of insulin allowed better characterization of irregular pulses because of the shorter half-life of insulin relative to C-peptide. The new modification of sequential eu- and hypoglycaemic clamp procedures should also be useful in pharmacological studies of insulinotropic substances. Direct measurement of peripheral insulin may be more sensitive than C-peptide to detect low levels of autonomous insulin secretion in small insulinomas.

Adult↗
PubMed2001

Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa.

BACKGROUND: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa. METHODS: Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. RESULTS: Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication. CONCLUSIONS: The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.

Adult↗