Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2.

A Thr789Ala variant in the von Willebrand Factor (vWF) gene is associated with increased vWF plasma concentrations and might therefore affect the risk of coronary heart disease (CHD) in the general population. Patients with type 2 diabetes have an increased risk for premature atherosclerosis and are characterized by alterations of the coagulation system. However, it is not known whether the Thr789Ala variant in the vWF gene contributes to the increased CHD risk in patients with type 2 diabetes. We therefore investigated the potential relationship between the Thr789Ala variant in the vWF gene and the occurrence of CHD in 356 patients with type 2 diabetes, either with (DM+/CHD+, n = 204) or without evidence for CHD (DM+/CHD-, n = 152). In addition, two control groups without type 2 diabetes, with (DM-/CHD+, n = 22) or without CHD (DM-/CHD-, n = 100), were investigated. Individuals with the vWF Thr789Ala variant have significantly higher von Willebrand factor plasma concentrations (p < 0.001). In addition, ristocetin co-factor was significantly increased in vWF Thr789Ala variant carriers (p < 0.05). Ristocetin co-factor levels and collagen binding capacity were also increased in individuals affected with either type 2 diabetes, CHD or both (DM+/CHD+, DM+/CHD-, DM-/CHD+) as compared to healthy controls (DM-/CHD-) (p < 0.001). However, we did not find an association between the vWF Thr789Ala variant and the occurrence of CHD in patient with type 2 diabetes (p = 0.34). In conclusion, although the Thr789Ala vWF gene variant is associated with increased plasma concentrations of vWF, ristocetin co factor levels and collagen binding capacity in patients with type 2 diabetes and CHD, a direct effect of this variant on the occurrence of CHD in patients with type 2 diabetes, could not be detected.

[Systematics of imaging artifacts in MRT caused by metallic vascular implants (stents)]. / Systematik der Artefakte metallischer Gefässprothesen (Stents) in der MRT.

PURPOSE: Imaging artifacts in magnetic resonance tomography (MRT) caused by metallic vascular implants (stents) were characterized systematically in dependence on the material and the construction of the implants as well as with respect to different measurement protocols and for different static field strength B (0). METHODS: Twelve stents, different in material (stainless steel, nitinol, Co-alloy) and/or construction, were examined at B (0) = 0.2 T and 1.0 T with two 2D gradient echo (GE) sequences (TE = 4 and 10 ms), one 3D GE sequence and one spin echo (SE) sequence. The stents were put into water with Gd-DTPA contrast agent. The dependence on the orientation was analyzed for the 9 possibilities of an orthogonal alignment of the stent axis, the direction of B (0), the slice, the read out, and the phase encoding direction. Special interest was given to the visibility of the stent lumen at forced rf excitation, as well as to the influence of broken struts on the signal obtained. RESULTS: For the examined stents GE technique showed, due to spin dephasing regions a total signal loss ranging up to 8 mm away from the stent mashes. The value depends on the stent material, the stent orientation in the scanner and grows with voxel size, echo time and B (0). In SE technique dephasing artifacts vanish and wrong spatial encoding gets visible, rf shielding is more pronounced. The visibility of the stent lumen ranges from nearly unperturbed down to a complete signal loss. An improvement is possible using enlarged flip angles. Broken struts can not be imaged significantly. DISCUSSION: The MR representation of metallic stents commercially available at the time, especially of nitionol stents, can be optimized with a suitable adaptation of the imaging parameters. However, a profound improvement can only be expected from new stent material and design.

No association between the angiotensin-converting-enzyme gene insertion/deletion polymorphism and the occurrence of macroangiopathy in patients with diabetes mellitus type 2.

Previous studies have reported an association between the ACE-I/D-polymorphism and coronary heart disease (CHD) in patients with diabetes mellitus. However, ACE inhibitor treatment, which could have compensated for negative effects of the D/D form of the ACE gene polymorphism, was not considered in the studies. We investigated the influence of the ACE-I/D polymorphism and the ACE inhibitor treatment in patients with diabetes mellitus on the occurrence of CHD by multiple-regression analysis. Distribution of the ACE gene I/D-polymorphism was investigated in 691 patients with diabetes mellitus prospectively characterised for the presence/absence of coronary heart disease. The distribution of DD; ID; II genotypes was 105 vs. 202 vs. 102 (25.7 % vs. 49.4 % vs. 24.9) in the CHD + group and 55 vs. 160 vs. 67 (19.5 % vs. 56.7 % vs. 23.8 %) in the CHD - group, respectively (p = 0.1). A multiple logistic regression analysis introducing the typical risk factors for CHD (age, gender, smoking, BMI > 26 kg/m 2, LDL elevation, HbA1c > 7 %) could not identify the ACE gene I/D-polymorphism as an independent risk factor for CHD (p = 0.87). Our data therefore suggest that the ACE gene I/D polymorphism is not associated with the occurrence of diabetic macroangiopathy in patients with or without treatment of ACE inhibitors.

Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus.

OBJECTIVE: Recent evidence indicates that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed at high levels in foam cells of atherosclerotic lesions, that PPARgamma agonists may directly modulate vessel wall function and that mutations in the PPARgamma-2 gene are associated with a reduced risk of coronary artery disease. METHODS: We investigated whether known variants in the PPARgamma-2 gene are associated with the occurrence of coronary heart disease (CHD) in 365 patients with type 2 diabetes, prospectively characterised for the presence or absence of CHD. The Pro115Gln, Pro12Ala, Pro467Leu, Val290Met mutations and two polymorphisms C478T and C161T of the PPARgamma-2 gene were examined using PCR, denaturing gradient gel electrophoresis and direct sequencing. RESULTS: The distribution of the Pro12Ala, Ala12Ala, C161T and T161T variants was not significantly different between patients with and without CHD, independent of the gender. The Pro12Ala (P=0.011) and the Ala12Ala (P=0.006) variant were associated with a higher body mass index (BMI) compared with the Pro12Pro genotype. A multiple logistic regression analysis introducing the typical risk factors for CHD (age, sex, hypertension, smoking, BMI >26 kg/m2, elevated low density lipoprotein cholesterol and haemoglobin A1c >7%) identified age >60, male gender, hypertension and a higher BMI, but not the PPARgamma-2 variants, as significant risk factors for CHD in our study groups. CONCLUSION: The PPARgamma-2 genotype was not associated with an increased or reduced risk of the occurrence of CHD and can therefore not be regarded as an independent risk factor for CHD in patients with diabetes mellitus.

Search for mitochondrial DNA mutation at position 3243 in German patients with a positive family history of maternal diabetes mellitus.

Mitochondrial diabetes is one of the most common monogenetic forms of diabetes mellitus. However, variable prevalences have been reported by different investigators. Therefore, the aim of our study was to investigate the prevalence of the most prevalent mitochondrial DNA mutation at position 3243 (A --> G) in german patients with a positive family history of maternally inherited diabetes mellitus and/or hearing loss. We screened 1460 patients with diabetes mellitus by a questionnaire and identified 122 patients with a positive family history of maternal diabetes mellitus. Seven of the 122 patients suffered from hearing loss in addition. An EDTA blood sample of each patient was examined by polymerase chain reaction followed by a digestion with Bsp120I. In addition all samples were further examined by denaturing gradient gel electrophoresis to increase the detection limit for heteroplasmy. Only one mt DNA mutation at position 3243 could be detected in the 122 patients. The detection limit of denaturing gradient gel electrophoresis (DGGE) for heteroplasmy was 3%. We detected one new polymorphism at position 3333 (C --> T) of the mitochondrial genome (0.8% of the patients), and a known polymorphism at position 3197 (T --> C) in 10.6% of the patients. We therefore conclude that the frequency of the A3243G mutation is much lower in the investigated study population, mostly originating from Saxonia, than in asian populations.

MR imaging in the presence of vascular stents: A systematic assessment of artifacts for various stent orientations, sequence types, and field strengths.

A systematic evaluation of the potential quality of magnetic resonance images recorded in the presence of metallic stents was performed on a low-field open imager operating at 0.2 T and on a high-field closed unit operating at 1.0 T. Eight different stent types were examined by two-dimensional gradient-echo sequences with echo times of 4 and 10 msec and by a fast spin-echo technique. In addition, a three-dimensional gradient-echo sequence was applied with an echo time of 2.4 msec. A set of sequence and slice parameters was used on both scanners. Thus, artifacts due to susceptibility effects depending on the magnetic field strength could be distinguished from radiofrequency shielding effects in the lumen of the stents (independent of the field strength). Nine different orthogonal orientations of the stent axis and the image (in terms of slice, read, and phase-encoding direction) were tested, and the artifacts (extension of signal void and visibility of the lumen) were compared. The optimal strategy for visualization of vascular and perivascular regions outside the stents was fast spin-echo imaging with the stent axis and read direction parallel to the static field. Susceptibility-induced signal void in gradient-echo images was minimal using the three-dimensional approach. Increased transmitter amplitudes above usual values provided clearly improved insight in the lumen using gradient-echo sequences.

[Possible genetic causes for late complications of diabetes mellitus]. / Mögliche genetische Ursachen für Spätkomplikationen des Diabetes mellitus.

BACKGROUND: Hyperglycemia occurs in every patient with diabetes mellitus. It is the most important factor in the development of diabetic complications. However, the onset, intensity and the progression of complications show large interindividual variations. Manifestation in families and the lack of complications in some diabetics with poor metabolic control indicate a genetic predisposition to develop diabetic complications like nephropathy, neuropathy and angiopathy. NEPHROPATHY: Diabetic nephropathy occurs only in 25 to 40% of the diabetic patients. Therefore a genetic risk factor for this complication is very likely. Various variations in genes like ACE-gene and angiotensinogen-gene have been described, which could be associated with the development of diabetic nephropathy. NEUROPATHY: Peripheral diabetic neuropathy occurs in up to 66% of all diabetics. Therefore and because of the possible pathological mechanisms genetic risk factors like variations in the Na/K-ATPase-gene and in the aldose reductase-gene are discussed. RETINOPATHY: An association between diabetic retinopathy and polymorphisms in the ACE-gene and the aldose reductase-gene seems very unlikely, because up to 75% of the diabetic patients suffer from retinopathy after 15 years of diabetes. MACROANGIOPATHY: A large number of studies show an association between diabetic macroangiopathy and genetic variations in the ACE-gene (I/D-variant) and the paraoxonase-gene (2 isoforms). CONCLUSION: Based on the current evidence for associations of genetic markers with diabetic complications, the generation of an individual risk profile based on genetic markers seems to be possible. In addition to near euglycemia genetic markers could direct therapeutic strategies and lead to new therapeutic approaches.

Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.

[Growing septum pellucidum cyst in infancy]. / Wachsende Septum Pellucidum Zyste im Säuglingsalter.

We report a baby's development with expanding cyst of the septum pellucidum. It was detected accidentally during diagnostic evaluation of epileptic convulsions and psychomotoric retardation. The dramatic increasing of the cyst was followed by cranial ultrasonography for ten months. The progression of clinical symptoms couldn't be explained because after drainage of the cyst, no improvement took place. MRT with Spectroscopy lead to the tentative diagnosis, Morbus Alexander. This couldn't be proved because no biopsy of the brain was performed against the decision of the child's mother, nor postmortal (the child died at 20 months).

Nitric oxide mediated formation of cyclic GMP in the olfactory system.

Olfactory cilia preparation from rats contain considerable activity of soluble guanylate cyclase as indicated by the formation of cyclic GMP (cGMP) upon application of nitroprusside, a nitric oxide generating agent. Stimulation of olfactory cilia with high doses of odorants elicited a delayed and sustained elevation of the cGMP-concentration. The odorant-induced cGMP-response was abolished by L-NG-nitro-arginine, a selective inhibitor of nitric oxide synthesis, as well as by haemoglobin which efficiently binds and inactivates nitric oxide. These observations suggest that the NO/cGMP cascade may plan an important role in signal processing of the olfactory system.

[Neonatal heart tumor. Early symptom of tuberous sclerosis]. / Neonataler Herztumor. Frühsymptom der tuberösen Sklerose.

Congenital heart tumors are rare. About 60% of them are intramurally growing rhabdomyomas. They represent an early symptom of tumerous sclerosis in about 50% of patients. The following report shows that fetal brady arrhythmia led towards the correct diagnosis.

[Spinal sonography of a newborn infant with postpartal paraplegia]. / Spinale Sonographie eines Neugeborenen mit postpartaler Querschnittssymptomatik.

Cranial ultrasonography is a well established diagnostic procedure. In contrast ultrasonography of the spine and the spinal cord is less frequently used. It is indicated in infants with spinal dysraphism and may help to diagnose patients with meningomyelocele, spinal lipoma or cord tethering. We present a newborn with parplectic symptoms as a result of an epidural hematoma, which could be demonstrated exclusively by ultrasonography. We want to stress that spinal ultrasonography is a method of high clinical value.

Mesomelic dysplasia, type Langer--a homozygous state for dyschondrosteosis.

Both parents of a female infant with mesomelic dysplasia, type Langer, showed signs of dyschondrosteosis. This further observation suggests that this type of mesomelic dysplasia may be due to homozygosity for the autosomal dominant gene of dyschondrosteosis.

[Interstitial pneumonia in children with acute lymphoblastic leukemia. prophylaxis with pentamidine during induction chemotherapy (author's transl)]. / Die interstitielle Pneumonie bei Kindern mit akuter lymphoblastischer Leukämie. Prophylaxe mit Pentamidine während der Induktionsbehandlung.

The influence of pentamidine prophylaxis on incidence and degree of interstitial pneumonia (IP) during a standardized induction chemotherapy in 100 children with acute lymphoblastic leukemia has been investigated. For radiologic evaluation we established three stages of IP. With pentamidine prophylaxis the incidence of IP was reduced from 48% to 9%. In addition, there was a significant reduction of severe or lethal courses.

The Roberts' syndrome.

A report is given on a small-for-date male infant showing the following symptoms: bilateral aplasia of humerus, radius, and ulna, shortened femora, bilateral cleft lip and cleft palate, stigmata of dysmorphism, and notably; simple helix formation of the ear, simian crease, clinodactylia, bilateral clubfoot deformity, hypospadia, thrombocytopenia, micrognathia, and contractures in the knee joints. Postmortem autopsy revealed horsehoe kidney, ureterstenosis with hydronephrosis, persistent branchial arches, and absence of the knee joints. Chromosome analysis results performed by G-band technique turned out normal. This, obviously, was a case of the so-called Roberts' syndrome. Our results were compared with the relevant literature and some particularities were emphasized. The question was discussed as to whether the SC-phocomelia (pseudothalidomid syndrome), the TAR syndrome, and reported single cases might be an identical syndrome.

[Mineral content of growing bone (author's transl)]. / Der Mineralgehalt des wachsenden Knochens

Normal mineral content of the calcaneus was determined in 137 healthy persons aged 3 to 20 years. Calcium-salt content increased with age, reaching 60% of its final value in the sixth year of life. In females mineralisation was practically complete in the 15th year.