Biguanides enhance glucose utilization and insulin action in peripheral tissues: an old finding from the sixties of the last century.
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Biomedical subjects
Publications and source records attributed to H Schatz.
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Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules.
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Nuclei with magic numbers serve as important benchmarks in nuclear theory. In addition, neutron-rich nuclei play an important role in the astrophysical rapid neutron-capture process (r process). 78Ni is the only doubly magic nucleus that is also an important waiting point in the r process, and serves as a major bottleneck in the synthesis of heavier elements. The half-life of 78Ni has been experimentally deduced for the first time at the Coupled Cyclotron Facility of the National Superconducting Cyclotron Laboratory at Michigan State University, and was found to be 110(+100)(-60) ms. In the same experiment, a first half-life was deduced for 77Ni of 128(+27)(-33) ms, and more precise half-lives were deduced for 75Ni and 76Ni of 344(+20)(-24) ms and 238(+15)(-18) ms, respectively.
The mass of one of the three major waiting points in the astrophysical rp process 72Kr was measured for the first time with the Penning trap mass spectrometer ISOLTRAP. The measurement yielded a relative mass uncertainty of deltam/m=1.2x10(-7) (deltam=8 keV). (73,74)Kr, also needed for astrophysical calculations, were measured with more than 1 order of magnitude improved accuracy. We use the ISOLTRAP masses of 72-74Kr to reanalyze the role of 72Kr (T(1/2)=17.2 s) in the rp process during x-ray bursts and conclude that 72Kr is a strong waiting point delaying the burst duration with at least 80% of its beta-decay half-life.
A new experimental approach was developed that can reduce the uncertainties in astrophysical rapid proton capture (rp) process calculations due to nuclear data. This approach utilizes neutron removal from a radioactive ion beam to populate the nuclear states of interest. Excited states were deduced by the gamma-decay spectra measured in a semiconductor Ge-detector array. In the first case studied, 33Ar, excited states were measured with uncertainties of several keV. The 2 orders of magnitude improvement in the uncertainty of the level energies resulted in a 3 orders of magnitude improvement in the uncertainty of the calculated 32Cl(p,gamma)33Ar rate that is critical to the modeling of the rp process. This approach has the potential to measure key properties of almost all interesting nuclei on the rp-process path.
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The main problems in the treatment of diabetic foot ulcers are prolonged wound healing and not necessary amputations, which may sometimes be caused by the impression that the results of conservative treatment are somewhat unpredictable. The aim of this study was to determine the effects of ulcer size on the wound radius reduction and healing times using a previously established equation for wound healing in neuropathic diabetic foot ulcers. This prospective study evaluates wound healing in 120 diabetic patients with neuropathic foot ulcers who were grouped according to four different ulcer areas (A 100 150 200 mm (2)). Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing in the different groups was compared by the weekly wound radius reduction using the equation R = sqrt A/pi. The average healing time in group A was 70 (95 %-CI 64 - 77) days with a wound radius reduction of 0.42 mm/week (95 %-CI 0.28 - 0.56). In group B the average healing time was 79 (95 %-CI 75 - 82) days and the weekly wound radius reduction was 0.47 mm (95 %-CI 0.45 - 0.49). The average healing time in group C was 85 (95 %-CI 80 - 89) days with a wound radius reduction of 0.53 mm/week (95 %-CI 0.42 - 0.56). In group D the average healing time was 97 (95 %-CI 91 - 103) days. The weekly wound radius reduction was 0.57 mm (95 %-CI 0.49 - 0.81). Wound radius reductions and the time needed for healing are affected by the ulcer area, a measure of ulcer size, in neuropathic diabetic foot ulcers. The calculation of the weekly wound radius reduction for different ulcer areas may be a useful tool in daily clinical practice to identify ulcers who do not respond adequately to the treatment.
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OBJECTIVES: Antibodies against granulocyte colony stimulating factor are frequently found in patients with Felty's syndrome (FS). In this study, we examined the prevalence of antibodies against two other granulopoietic cytokines: granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL3). METHODS: Sera of 32 patients with FS, 20 normocytic patients with rheumatoid arthritis (RA), and 72 healthy individuals were screened for the presence of antibodies against GM-CSF and IL3 by ELISA and bioassays, using the human erythroleukaemia cell line TF-1. RESULTS: In two of the 32 patients with FS, antibodies to GM-CSF and IL3 were detectable by ELISA. Binding anti-GM-CSF antibodies were also detected in one of the 72 healthy controls, while in another healthy subject and in one of the patients with normocytic RA, anti-IL3 antibodies were present. Serum from one of the two patients with FS who tested positive for anti-IL3 and anti-GM-CSF antibodies by ELISA showed strong neutralising capacity to the biological effect of IL3, but not to GM-CSF in vitro. Patients with FS had significantly higher serum levels of GM-CSF (median; 2.82 pg/mL; interquartile range 2.64-3.19 pg/mL) compared with patients with RA (2.52 pg/mL; 2.28-2.72 pg/mL; p = 0.012) and healthy controls (2.23 pg/mL; 2.04-2.52; p<0.001). In addition, serum levels of IL3 in patients were significantly higher in FS (10.05 pg/mL; 8.94-11.98) compared with controls (4.79 pg/mL; 3.72-7.22; p<0.001), but not compared with RA patients (9.52 pg/mL; 8.32-10.42; p = 0.17). CONCLUSIONS: Antibodies to GM-CSF and IL3 are rare in patients with FS and RA and in healthy subjects. In individual patients with FS, the presence of neutralising anti-IL3 antibodies may contribute to the development of cytopenia.
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We report the case of a 41-year-old female patient with relapsing polychondritis and severe respiratory involvement. The patient presented with acute respiratory failure requiring endotracheal intubation. Bronchoscopy revealed tracheal collapse and inflammatory stenoses with dynamic collapse of the major airways. We describe a multidisciplinary therapeutic approach, consisting of immunosuppressive treatment, bronchoscopic placement of self-expandable stents into the collapsing bronchi, and tracheotomy. In addition, we report the effectiveness of oral cyclophosphamide for treatment of relapsing polychondritis with severe respiratory involvement after failure of other immunosuppressive agents. The problem of severe respiratory complications in patients with relapsing polychondritis and the need for a multidisciplinary approach is discussed.
Impairment of 0.1-Hz vasomotion, which was found in diabetic patients, was suggested to be an early index of sympathetic dysfunction. We studied the relationships between alterations in vasomotion and both cardiac autonomic and sensory neuropathy. Twenty type 1 and 22 type 2 diabetic patients were investigated. Vasomotion was recorded in single capillaries at the dorsal middle phalangeal area of the left ring finger by means of laser Doppler anemometry. Cardiac autonomic neuropathy was assessed by spectral analysis of heart rate variation during rest and recording heart rate responses to deep breathing and Valsalva manoeuvre. Sensory neuropathy was investigated by measuring heat pain, vibration, and thermal sensory thresholds. Impaired vasomotion was more often (82.4%) found in diabetic patients with at least one altered cardiac autonomic test, but also in 47.1% of those with all of these tests being normal (P = 0.035). Both heart rate variation coefficient during rest (r = 0.40, P = 0.045) and Valsalva ratio (r = 0.41, P = 0.037) correlated positively with amplitudes of vasomotion in type 1 diabetic patients. The prevalence of impaired vasomotion was not higher in patients with sensory neuropathy compared to those with normal sensory functions. A disturbed warm sensation was only found in 2 patients and none had an abnormal heat pain threshold. Our data indicate that impairment of 0.1-Hz vasomotion precedes parasympathetic neuropathy, assessed by heart rate variation tests, and abnormalities in warm and heat pain sensation. Reduction of arteriolar vasomotion, detected by laser Doppler anemometry, might be an early index of sympathetic dysfunction, because it correlates with disturbances in those cardiac autonomic tests, which are at least in part under sympathetic control.
Ca(2+)/calmodulin-dependent protein kinase II is a member of a broad family of ubiquitously expressed Ca(2+) sensing serine/threonine-kinases. Ca(2+)/calmodulin-dependent protein kinase II is highly expressed in insulin secreting cells and is associated with insulin secretory granules and has been proposed to play an important role in exocytosis or in insulin granule transport to release sites. To elucidate its function the antisense sequence of the major beta-cell subtype, Ca(2+)/calmodulin-dependent protein kinase II delta(2), was stably expressed in INS-1 rat insulinoma cells. This caused a loss of Ca(2+)/calmodulin-dependent protein kinase II delta(2) expression at the mRNA and protein level, while the expression of the 95% homologous Ca(2+)/calmodulin-dependent protein kinase II gamma and of beta-cell specific proteins such as the homeodomain factor pancreatic-duodenal homeobox factor-1 (PDX-1, also referred to as islet/duodenum homeobox-1, IDX-1, insulin promoter factor-1, IPF-1 and somatostatin transactivating factor-1, STF-1), the glucagon-like peptide-1 (GLP-1) receptor and K(ATP)-channels K(IR)6.2/SUR-1 (sulfonylurea receptor-1) was not altered. Unexpectedly, the cells showed a large reduction of insulin gene expression, which was due to reduced insulin gene transcription. Electrophoretic mobility shift assays of PDX-1 binding to the insulin promoter A1 and E2/A3A4 elements showed additional bands indicating alterations of PDX-1 complex formation. Stable over expression of Ca(2+)/calmodulin-dependent protein kinase II delta(2), by contrast, was associated with elevated expression of insulin mRNA. Therefore, we conclude that Ca(2+)/calmodulin-dependent protein kinase II delta(2) links fuel-dependent increases in intracellular Ca(2+) concentrations to transcriptional regulation of genes related to the metabolic control of insulin secretion.
AIMS: The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers, but knowledge of its effects on wound healing is sparse. The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a standard method of plantar pressure relief. MATERIALS AND METHODS: A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospective randomized controlled study. 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; 24 patients were randomized to the felted foam therapy, and 30 patients were randomized to conventional therapy. RESULTS: In the felted foam group, the initial average wound area was 102.3 +/- 45.3 mm2 (mean +/- sd), and 5.4 +/- 3.1 mm2 after 10 weeks with an average healing time of 75 days [95% confidence interval (CI) 67-84]. In the conventional therapy group, the initial average wound area was 112.5 +/- 50.8 mm2, and 10.6 +/- 4.2 mm2 after 10 weeks with an average healing time of 85 days (95% CI 79-92) (P = 0.03). The mean wound radius decreased by 0.48 mm (95% CI 0.42-0.56) per week in the felted foam group and by 0.39 mm (95% CI 0.35-0.42) per week in the conventional group (P = 0.005). CONCLUSIONS: The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment. It may be a useful alternative in treating neuropathic foot ulceration, especially in patients who are not able to avoid weight-bearing reliably.
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Arteriolar vasomotion, the cyclic contraction/dilation of terminal arterioles, is disordered in diabetes. The aim of the present study was to characterize the impairment of cutaneous vasomotion in type 1 and type 2 diabetes, especially with regard to the influence of metabolic control and to the response to shear stress. Twenty type 1 and 23 type 2 diabetic patients were investigated. Vasomotion waves were recorded in single capillaries at the dorsal middle phalangeal area of the left ring finger during rest, after warming the skin temperature to 33 degrees C, and after 3-min arterial occlusion by means of laser Doppler anemometry. Suprasystolic occlusion caused an increase in amplitudes of vasomotion only in type 1 diabetic patients (0.12 +/- 0.04 mm/s vs. 0.36 +/- 0.06 mm/s, p = 0.001). In type 1 but not in type 2 diabetic patients, both systolic and diastolic blood pressure correlated positively with amplitudes of resting vasomotion (r = 0.62, p = 0.002 and r = 0.65, p = 0.001, respectively). Amplitudes of vasomotion after warming up at frequencies of 5 - 8 cycles per minute (0.08 - 0.13 Hz) correlated inversely with the levels of glycated hemoglobin (HbA 1c ) (r = - 0.56, p = 0.005) only in type 1 diabetic patients. In conclusion, we found suprasystolic occlusion and increasing blood pressure to provoke vasomotion with a concomitant decrease in effective vascular resistance only in type 1 diabetic patients. The impaired vasomotion response to shear stress in type 2 diabetes might favour the development of skin lesions and arterial hypertension. Insufficient glycemic control seems to be an important factor in the pathogenesis of impaired vasomotion in type 1 diabetes.
Hypochondroplasia is a clinically and genetically heterogeneous skeletal dysplasia with less obvious disproportion in childhood and a reduced pubertal growth spurt. We report on a young hypochondroplastic man who had been misdiagnosed and treated as being growth hormone (GH) deficient in the early phase of puberty. The delay of his puberty which is unusual in hypochondroplasia might have confused the results of provocative GH testing. At the age of 17 years measurement of body proportions revealed an increased upper to lower body segment ratio. Skeletal radiographs showed a lack of increase in the interpedicular distance from the first to the fifth lumbar vertebra, anteroposterior shortening of the lumbar pedicles, short femoral necks, a fibula longer than the tibia, and short tubular bones. As the clinical and radiographic features suggested the diagnosis of a skeletal dysplasia, a DNA sequence analysis of the fibroblast growth factor receptor 3 gene on chromosome 4 p16.3 was performed, which identified the missense mutation C1620 G in the tyrosine kinase domain resulting in an Asn540Lys substitution. Hypochondroplastic children with this common mutation (N540K) were previously found to respond to GH treatment with an increase in sitting height compared to leg length, which accentuated the existing disproportion. We want to emphasise that in children with normal serum IGF-I and IGFBP-3 levels accurate measurements of body proportions and skeletal radiographs in disproportionate cases are more important than reiterative GH stimulation tests, which prepubertally and in the early phase of puberty often show subnormal responses.