Screening for renal insufficiency following ESUR (European Society of Urogenital Radiology) guidelines with on-site creatinine measurements in an outpatient setting.

OBJECTIVE: To report the results and implications for workflow following introduction of ESUR guidelines to screen for potential renal insufficiency (RI) in private practice with on-site creatinine measurements. METHODS: A total of 1,766 consecutive outpatients scheduled for contrast-enhanced CT (CECT) completed the ESUR questionnaire enquiring about kidney disease, renal surgery, proteinuria, diabetes mellitus, hypertension, gout or use of nephrotoxic drugs. Patients with positive risk factors underwent on-site creatinine measurement and calculation of estimated glomerular filtration rate (eGFR). Attending radiologists adapted subsequent imaging depending on renal function and presence of risk factors. RESULTS: One or more ESUR risk factors were present in 796 (45.1%) patients, including hypertension (37.7%), nephrotoxic medication (21.3%), diabetes mellitus (8.0%), proteinuria (3.9%), renal disease (4.1%), gout (3.1%) and renal surgery (2.6%). Pre-procedural creatinine measurements revealed severe RI (eGFR < 30 ml min(-1) 1.73 m(-2)) in 10 (1.3%) and moderate RI (eGFR 30-59 ml min(-1) 1.73 m(-2)) in 106 (13.8%). Imaging work-up was adapted in 132 (16.6%) as follows: reduction of contrast material dose (n = 85), CT without contrast (n = 40), changeover to MRI (n = 3) or scintigraphy (n = 4). CONCLUSION: Screening for RI following ESUR guidelines requires creatinine measurements in nearly half of outpatients scheduled for CECT and reveals moderate to severe renal impairment in 6.6%.

Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.

We have recently shown that mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). Here, we report the exon-intron organization and partial sequence of the human HNF-1alpha gene. In addition, we have screened the ten exons and flanking introns of this gene for mutations in a group of 25 unrelated white subjects from Germany who presented with NIDDM before 35 years of age and had a first-degree relative with NIDDM. Mutations were identified in nine of these individuals, suggesting that mutations in the HNF-1alpha gene are a common cause of diabetes in German subjects with early-onset NIDDM and a family history of diabetes. Thus, screening for mutations in this gene may be indicated in subjects with early-onset NIDDM. Interestingly, three of the nine mutations occurred at the same site in exon 4 with insertion of a C in a polyC tract, centered around codon 290 (designated Pro291fsinsC), thereby resulting in a frameshift during translation and premature termination. Analyses of linked DNA polymorphisms in the HNF-1alpha gene indicated that the Pro291fsinsC mutation was present on a different haplotype in each subject, implying that the polyC tract represents a mutational hot spot. We have also identified the mutation in the HNF-1alpha gene in the Jutland pedigree, one of the original MODY pedigrees reported in the literature, as being a T-->G substitution in codon 241, resulting in the replacement of a conserved Cys by Gly (C241G). The information on the sequence of the HNF-1alpha gene and its promoter region will facilitate the search for mutations in other subjects and studies of the role of the gene in determining normal beta-cell functions.

Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study).

OBJECTIVE: The aim of the study was to evaluate the efficacy of benfotiamine administered over three weeks (allithiamine; a lipid-soluble vitamin B1 prodrug with high bioavailability) to patients with diabetic polyneuropathy in a randomized, placebo-controlled, double-blind, two-center pilot study. MATERIAL AND METHODS: Forty inpatients (23 male, 18 female, age range 18 - 70 years) with a history of type 1 or 2 diabetes and polyneuropathy of not longer than two years, were included in the study. Twenty Patients received two 50 mg benfotiamine tablets four times daily and 20 patients received placebo over the three-week study period. Two clinical units were involved with 10 patients receiving placebo and 10 patients benfotiamine in each. The neuropathy score according to Katzenwadel et al. [1987] was used to evaluate symptoms of polyneuropathy, vibration perception threshold and both the physician's and the patient's own assessment were documented. RESULTS: A statistically significant (p = 0.0287) improvement in the neuropathy score was observed in the group given active drug when compared to the placebo-treated controls. There was no statistically significant change observed in the tuning fork test. The most pronounced effect on complaints was a decrease in pain (p = 0.0414). More patients in the benfotiamine-treated group than in the placebo group considered their clinical condition to have improved (p = 0.052). No side effects attributable to benfotiamine were observed. The differences between the groups cannot be attributed to a change in metabolic parameters since there were no significant alterations in the HbA1 levels and blood sugar profiles. The body mass index of the two groups did not differ. CONCLUSION: This pilot investigation (BEDIP Study) has confirmed the results of two earlier randomized controlled trials and has provided further evidence for the beneficial effects of benfotiamine in patients with diabetic neuropathy.

Elevated lipoprotein lipase activity in skeletal muscle tissue during treatment of hypertriglyceridaemic patients with bezafibrate.

Eleven hypertriglyceridaemic patients were treated with 600 mg bezafibrate daily for 2 months. The mean serum triglyceride concentration decreased by 35% (P less than 0.01) corresponding to a reduction in the very low density lipoprotein triglycerides by 41% (P less than 0.01). The high density lipoprotein cholesterol concentration and the serum concentration of apolipoproteins AI and AII increased by 19% (P less than 0.02), 11% (N.S., P less than 0.08) and 24% (P less than 0.01), respectively. The fractional removal rate (K2) in the intravenous fat tolerance test (IVFTT) increased by 37% (P less than 0.001). This was associated with significant increase of the skeletal muscle lipoprotein lipase activity ( + 39%, P less than 0.05). The mean value for the adipose tissue lipoprotein lipase activity remained unchanged. The K2 at IVFTT was correlated highly significantly to the activity of skeletal muscle lipoprotein lipase (r = 0.85, P less than 0.01). The present study indicates that the main reason for the reduction of the serum triglycerides during treatment with bezafibrate may be an increased activity of the skeletal muscle tissue lipoprotein lipase activity.

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.

Sedative properties of doxepin in comparison with diazepam.

Doxepin (Quitaxon) at doses of 25, 50, and 75 mg was compared with diazepam 7.5, 15, and 22.5 mg, using as variables the percentage lowering of Critical Flicker Fusion (CFF) and the self-estimated degree of drowsiness. Single doses were given, and repeated effect determinations were made over 6 h. Clear dose-effect relations could be demonstrated. The two drugs differed in speed and duration of action and in steepness of effect increase with dose. Although there were good correlations between CFF effect and subjective drowsiness, it seemed that the two methods interrelated somewhat differently in the different types of drug. CFF was a more stable and reliable method than the subjective estimation of drowsiness. However, when comparing drugs belonging to different classes, both methods preferably should be used together.

Dual-isotope SPET 201Tl rest/99mTc-MIBI stress: one-day protocol for pre-operative myocardial imaging?

We compared the results of a rest 201TI/stress 99mTc-MIBI protocol, both by means of separate single isotope and simultaneous dual isotope acquisition, with a standard stress/rest 99mTc-MIBI 2-day protocol in 11 patients with low probability of CAD and 14 patients with chronic CAD. In patients with CAD 406 segments (sgs) were analysed. In the standard protocol 119 sgs were classified as pathological of which 50.4% were fixed and 49.6% reversible defects. With the MIBI-stress/TI-rest single 33% of 119 pathological sgs were fixed and 67% reversible defects. With the MIBI-stress/TI-rest dual only 20% were fixed and 80% reversible defects. The reversibility of 59 MIBI-stress/MIBI-rest reversible defects was quantified: MIBI-stress/MIBI-rest 35 +/- 16% MIBI-stress/TI-rest single 50 +/- 26% and MIBI-stress/TI-rest dual 48 +/- 22%. The results of 99mTc-MIBI rest and 201TI rest studies in patients with chronic CAD are not the same. Dual-isotope 1-day 201TI-rest/99mTc-MIBI-stress SPET data, acquired separately, may give fast and complete information on myocardial perfusion at stress and rest, respectively, and on myocardial viability.

MR imaging of the diabetic foot.

Diabetes is a common disease with potentially devastating complications affecting the foot and ankle. A combination of vascular disease, peripheral neuropathy, and immunopathy result in a cascade of conditions including ischemia/infarction, tendinopathy, atrophy, edema, deformity, neuropathic osteoarthopathy, callus, ulceration, and infection. The MR imaging appearance of these complications will be discussed. Recognition of these MR imaging patterns facilitates formulation of medical or surgical treatment plans.

MR imaging of inflammatory conditions of the ankle and foot.

Infection and noninfection inflammatory diseases commonly affect the foot and ankle; they have a significant impact on the cost of medical care and are a major source of referral for MR imaging evaluation. Recognition of the MR imaging appearance of the various manifestations of these disorders is important so that prompt and appropriate medical or surgical management can be instituted. This article emphasizes MR imaging of the most important diseases in this category, diabetic foot infection and the rheumatoid foot, but will also discuss manifestations in the foot and ankle of various other inflammatory diseases, such as gout and seronegative spondyloarthropathies.

Routine 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) myocardial tomography using a normal large field of view gamma-camera.

There is a recent need to study glucose metabolism of the heart in ischemic, as well as in "hibernating or stunned" myocardium, and compare it with that in perfusion studies. In non-positron emission tomography centers, positron imaging is possible with a standard Anger-type camera if proper collimation and adequate shielding of the camera crystal can be achieved. For the study with fast-decaying isotopes, seven-pinhole tomography (7PHT), a limited-angle method designed for transaxial tomography of the left ventricle using a nonrotating camera, is well suited, because projections are acquired simultaneously. Individual adjustment (patient supine) of the camera's view axis (CAx) with the left ventricular axis (LVAx) gives excellent results: sensitivity for CHD 82%, specificity 72% in a prospective 201TI study (48 patients, x-ray coronarography as reference). Good alignment of CAx with LVAx is also achieved with the patient prone in LAO in a hammock above the camera surface. In this setting additional lead shielding of the camera is possible using a table reinforced with 5 cm of lead with a central hole for the 7PH-collimator, which has a special lead inlay. This allows utilization of the 511 KeV emitter 18F-FDG, which with a half-life of 109 minutes, can be transported a reasonable distance from the production site. System sensitivity and resolution for 18F was found comparable to 201Tl, 99mTc, and 123I using a phantom. First clinical examinations after 201Tl stress/redistribution studies showed increased 18F-FDG uptake in ischemic heart segments, as well as in "hibernating" nonperfused or "stunned" myocardium.

Comparative pharmacokinetics of 400 mg bezafibrate after a single oral administration of a new slow-release preparation and the currently available commercial form.

Bezafibrate is a new lipid-lowering agent with a more pronounced pharmacological effect, a different metabolism and a much shorter apparent half-life than clofibrate. The serum concentration curves and the urinary excretion were determined in seventeen healthy volunteers after administration of 400 mg of a new slow-release preparation. The results were compared with those of a similar experiment in twenty healthy volunteers who received 400 mg as a single dose in the form of 2 tablets of Cedur, which is the currently marketed form in Germany (each tablet contains 200 mg bezafibrate). The areas under the serum concentration curves were not statistically significantly different (median of 31.3 mg . h/l for the slow-release and of 39.4 mg . h/l for the marketed preparation). Renal clearance differed only within the margin of biological variation. It can be assumed that the relative biological availability of both preparations is similar. In none of the volunteers were subjective or objective side-effects observed.

Effects of bezafibrate on low HDL-cholesterol in patients with ischaemic cerebrovascular disease: a pilot study.

Bezafibrate is a new lipid-lowering agent that quite constantly increases low HDL-cholesterol values in hyperlipoproteinaemic patients. The possible role fo HDL-cholesterol as an anti-atherogenic factor has been frequently discussed, mainly in patients with ischaemic heart disease but recently also in ischaemic cerebrovascular disease (ICD). This is the first pilot study in six selected patients suffering from ICD who had at the same time low HDL-cholesterol values (less than or equal to = 1.1 mmol/l) with otherwise normal lipids. After a wash-out period of 2 months duration these patients were treated with 200 mg bezafibrate t.i.d. for 2 months. They were then followed up for another 8 months. Bezafibrate therapy increased HDL-cholesterol (range 45-130%). Eight months after cessation of therapy five patients have returned to pathologically low HDL-levels and the sixth patient also has a relatively low value of 1.2 mmol/l. This small preliminary study cannot, however, provide evidence about the possible beneficial role of increasing HDL-cholesterol in patients with ICD. Further investigations are therefore in progress.

Magnetic resonance signal alterations in the acute onset of heterotopic ossification in patients with spinal cord injury.

The purpose of our study was to evaluate magnetic resonance (MR) signal characteristics of acutely forming heterotopic ossification (HO) in paralyzed patients. Fourteen patients with spinal cord injury (female n=2, male n=12, mean age 38.3 years) and acute onset of radiographically proven HO had contrast-enhanced 1.5-T MRI within 13.4+/-18.3 days of clinical onset of symptoms. MR signal alterations of affected muscles, fascia, subcutaneous tissue, skin and adjacent bone were evaluated. A diffuse T2-hyperintense signal of multiple muscle groups was seen in all patients (bilateral in 12) involving quadriceps (n=13, 93%), adductors (n=13, 93%) and iliopsoas (n=12, 86%) with contrast enhancement in n=11 (79%), n=8 (57%) and n=8 (57%) patients. All patients had nonenhancing areas (mean size 2 x 3.5 x 5.8 cm) within diffusely enhancing muscles. HO formation occurred around these nonenhancing areas in four patients with computed tomography follow-up. Other MR findings included fascial edema (n=14, 100%), fascial enhancement (n=13, 93%), subcutaneous edema (n=13, 93%), subcutaneous enhancement (n=12, 86%), bone marrow edema (n=5, 36%), and joint effusion (n=12, 86%). MRI reveals mostly bilateral edema and enhancement of muscles, fascia and subcutaneous tissue during acute onset of HO. HO develops in the periphery of well-defined areas of no enhancement.

[Effect of acarbose on postprandial increase in blood glucose. Additive acute effect of once daily administration in insulin treated diabetes]. / Wirkung von Acarbose auf den postprandialen Blutzuckeranstieg. Additiver Akuteffekt der einmal täglichen Gabe bei insulinbehandelten Diabetikern.

UNLABELLED: Only few controlled studies have been conducted on the influence of additive treatment with the glucosidase inhibitor acarbose on post-prandial blood sugar levels in insulin-dependent diabetics. To date, the behavior of blood sugar levels under treatment with acarbose has not been studied in insulin-dependent, type II diabetics. METHOD: Forty-six diabetics--36 insulin-dependent type II, and 10 type I--were enrolled in a double-blind, placebo-controlled randomized parallel group study with the aim of investigating the influence of acarbose on the primary variable maximum blood glucose increase following a standard breakfast eaten after 7 days of treatment. The patients were to have an HbA1 value of > 9%, and a post-prandial increase in blood glucose 90 minutes after a standardised breakfast (3 white bread units) of at least 50 mg/dl as compared with the fasting blood sugar during a one-week run-in period. INTERVENTION: The patients were randomized to treatment consisting of either one tablet of 100 mg acarbose or a single placebo tablet taken daily with breakfast. RESULTS: While the placebo group showed a mean further rise in maximum blood glucose levels after 7 days of treatment from 76.1 +/- 13.1 mg/dl to 84.3 +/- 17.8 mg/dl over the baseline value, there was a decrease in the acarbose group from 80.5 +/- 12.8 to 46.3 +/- 12.8 mg/dl. The difference between the two groups was statistically significant (p = 0.0001). No significant correlation was found between the treatment and type of diabetes. Mild adverse events such as meteorism, flatulence and diarrhea did not lead to any interruption of the study, and had cleared up by the end of the trial in all patients. CONCLUSION: The use of a single dose of 100 mg acarbose at breakfast time can result in a marked flattening of elevated post-prandial morning blood glucose profiles in both insulin-dependent type II and type I diabetics.

[Significance of the specialized treatment clinic for the rehabilitation of diabetic patients]. / Zur Bedeutung der spezialisierten Kurklinik für die Rehabilitation Zuckerkranker.

Since January 1, 1986 all our diabetes mellitus patients have participated in a structured diabetes education programme of two weeks duration. A systematic review of 260 diabetic patients treated by us up to June 30, 1987, has shown that only 25 (9.6%) had been suitably informed about their disease. Necessary therapeutic consequences, such as strict dietetic measures, additional insulin therapy or intensified conventional insulin therapy, were more readily understood and accepted after the education course. The basic conditions present in a specialized rehabilitation clinic are more favourable in view of good longterm metabolic control than in the acute hospital or in general practice.

Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers.

The cardiovascular effects of single oral doses of nifedipine (20 mg), atenolol (50 mg), or of their combination were compared with placebo in a double-blind randomized cross-over study in 10 normotensive volunteers. After subjects rested for 2 h, before drug administration, heart rate, blood pressure, stroke volume index, and cardiac index were measured noninvasively. These cardiovascular parameters were then determined prior to and after exercise periods (160 W, 10 min, bicycle ergometry) which were performed 40, 70, 130, 190, 310 min, and 22 h after drug intake. Nifedipine decreased resting diastolic blood pressure (p less than or equal to 0.05) after 2 h, whereas systolic blood pressure remained unchanged and heart rate significantly increased at rest and after exercise. Stroke volume index and cardiac index were unaffected. Atenolol significantly decreased systolic and diastolic blood pressure as well as heart rate; stroke volume index following exercise increased significantly, and cardiac index was unchanged. Administration of the combination caused a significantly more pronounced fall of systolic and diastolic blood pressure as compared with either drug alone, whereas the negative chronotropic effect was not different from that of atenolol. As did atenolol, the combination increased stroke volume index after exercise with no change in cardiac index. Maximum plasma concentrations of nifedipine (37.1 +/- 16.7 ng/ml) and atenolol (276.3 +/- 107.2 ng/ml) and terminal half-life of atenolol (9.9 +/- 2.6 h) were not altered by combined administration of the drugs.

Pitfalls and limitations of magnetic resonance imaging in chronic posttraumatic osteomyelitis.

The aim of this study was to evaluate pitfalls and technical limitations of MR imaging in diagnosing relapse of chronic posttraumatic osteomyelitis of the lower extremities. Retrospective analysis of MR examinations in 15 patients (17 body areas) with suspected relapse of chronic posttraumatic osteomyelitis (at least 1.5 years duration/mean number of surgical procedures per patient: 5.8). The MRI findings were compared with postoperative bacteriology (n = 11) and clinical follow-up (n = 4). Five patients had additional CT examination. Magnetic resonance imaging identified all infected areas correctly, but five uninfected regions were diagnosed false positive due to postoperative scarring/oedema in bone defects (n = 4) and soft tissue (n = 1). Specificity of MRI in diagnosing active bone infection was 63% and sensitivity 100%. Additional CT was preoperatively necessary in 5 patients (33%) to further examine osteomyelitic and reparative bone remodeling. Metal artefacts were present in 11 patients, rendering complete evaluation impossible (n = 2) or considerably more difficult (n = 4). Scarring/oedema in postoperative bone defects occurs up to 13 months postoperatively and represents a major pitfall leading to low specificity. Definitive evaluation of suspected fistula, bony fragments and mineralization by MRI may be limited in this special patient group and requires additional CT in one third of patients. Metal artefacts occur in most patients and may impair or even prevent correct film evaluation in 23 and 11%, respectively.