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Biomedical subjects

G J Krejs

Publications and source records attributed to G J Krejs.

At least 19 recordsLinked to original sources
PubMed2000

Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus.

AIMS: In intensified insulin therapy, the recent development of short-acting insulin analogues with a very rapid onset of action forces a new discussion in terms of the optimal injection-meal interval. This study evaluated prandial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of soluble human insulin (HI) and the insulin analogue insulin aspart (IAsp) at different injection-meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control. METHODS: In a randomized, double-blind, double-dummy, four-period crossover study, 20 Type 1 diabetic patients were investigated. Prandial insulin was administered 15 min before the start of the meal (HI(-15min)), immediately before the meal (HI(0min); IAsp(0min)) and 15 min after the start of the meal (IAsp(+15min)). RESULTS: Plasma glucose excursions from baseline levels during the 4 h (PGexc) were highest with HI(0min) (17.9 mmol.l(-1).h; P < 0.05 vs. other treatments) and were not statistically different for HI(-15min), IAsp(0min) and IAsp(15min) (13.6, 11.9 and 14.2 mmol.l(-1).h, respectively). Maximum concentration of plasma glucose (PGmax) was lowest with IAsp(0min) (11.2 mmol/l; P < 0.05 vs. other treatments). PGmax was comparable with HI(-15min), HI(0min) and IAsp(+15min) (13.3, 14.1 and 13.2 mmol/l, respectively). CONCLUSIONS: With regard to prandial glycaemia IAsp(+15min) is as effective as HI(-5min) and superior to HI(0min). Thus, post-prandial dosing of the insulin analogue IAsp offers an attractive and feasible therapeutic option for well-controlled patients with Type 1 diabetes mellitus.

Adult↗
PubMed2000

Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans.

NN304 is a long-acting insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH insulin. Thus, in contrast to animal studies NN304 and NPH insulin can not be considered equipotent in humans.

Adult↗
PubMed2000

Intra-hepatic haematoma complicating transjugular intra-hepatic portosystemic shunt for Budd-Chiari syndrome associated with anti-phospholipid antibodies, aplastic anaemia and chronic hepatitis C.

Portal venous decompression with transjugular intra-hepatic portosystemic shunt (TIPS) is a new approach in the treatment of Budd-Chiari syndrome. We report on a 31-year-old female with Budd-Chiari syndrome due to anti-phospholipid antibodies with compression of the inferior vena cava treated with TIPS and stenting of the inferior vena cava. TIPS was complicated by massive intra-hepatic haematoma which was managed conservatively. Treatment options and pathogenic mechanisms of Budd-Chiari syndrome under the rare coincidence of aplastic anaemia and anti-phospholipid syndrome are discussed. TIPS may be considered for venous decompression in Budd-Chiari syndrome, but physicians should be aware of potential TIPS' complications in these patients.

Adult↗
PubMed2000

Effects of postprandial walking on delayed gastric emptying and intragastric meal distribution in longstanding diabetics.

OBJECTIVE: We investigated the influence of standardized postprandial walking on the rates of gastric emptying and of intragastric meal distribution in 50 consecutive patients with longstanding insulin-dependent diabetes mellitus. METHODS: Gastric emptying of a semisolid meal labeled with 99mTc was continuously recorded with a dual-head gamma camera with patients in the supine position for 90 min before and 20 min after a 30-min postprandial walk. Regions of interest enclosing total stomach, and proximal and distal gastric compartments were calculated to determine gastric emptying rates and intragastric meal distribution. RESULTS: The evaluation of gastric emptying rates before and after postprandial walking demonstrated two variants of delayed gastric emptying: one variant that was counteracted by postprandial walking in seven patients (14%, Group I) and another variant that was not influenced by postprandial walking in 11 patients (22%, Group II). In addition, the emptying rates of 28 patients (56%) were within the range of controls and in four patients the emptying was accelerated (8%). The filling of the proximal gastric compartment was predominant and remained dominant after walking in Groups I and II. In controls and in diabetics with normal gastric emptying, the preliminary predominant filling of the proximal compartment was equalized after walking and the proximal compartment regained predominance thereafter. The changes in gastric emptying characteristics from delayed to accelerated gastric emptying may be related to the duration of diabetes (r = -0.47, p<0.03) and were not indicated by symptoms of upper GI discomfort or by secondary diabetic manifestations. CONCLUSION: Postprandial walking may improve gastric emptying in 14% of patients with longstanding insulin-dependent diabetes mellitus.

Adult↗
PubMed2000

Scintigraphic long-term follow-up of a patient with metastatic glucagonoma.

Two years after resection of a pancreatic glucagonoma, scintigraphy with 111indium-labeled octreotide revealed hepatic metastases in a 48-yr-old man. Hepatic metastases were also visualized by CT, whereas an additional lesion in the chest was seen only by scintigraphy. A total of 11 follow-up examinations over 46 months proved somatostatin receptor scintigraphy to monitor reliably somatostatin receptor expression, growth and dissemination of glucagonoma metastases, and to indicate therapeutic readjustment if necessary. The survival time of the patient is now >75 months, in comparison with a mean survival time of 59 months reported for metastatic glucagonoma.

Follow-Up Studies↗
PubMed2000

Evaluation of HbA1c determination methods in patients with hemoglobinopathies.

OBJECTIVE: To evaluate commercially available determination methods for HbA1c in patients with hemoglobin variants. RESEARCH DESIGN AND METHODS: HbA1c values were determined with various commercially available methods, including ion-exchange high-performance liquid chromatography (HPLC), boronate affinity assay, and immunoagglutination in patients with the hemoglobin mutations Hb Graz, Hb Sherwood Forest, Hb O Padova, Hb D, and Hb S. RESULTS: The effect of hemoglobinopathies on glycohemoglobin measurements was highly method dependent. The HPLC methods for HbA1c determination lacked the resolution necessary to differentiate hemoglobin variants. They demonstrated additional peaks in the chromatograms and HbA1c results either too low or too high compared with the nondiabetic reference range. With all immunoassays, Hb Graz demonstrated falsely low values. The other hemoglobinopathies in our study caused falsely low and/or high HbA1c results in immunoagglutination methods. The boronate affinity method showed values in an acceptable range for all hemoglobin variants. CONCLUSIONS: Because of the local occurrence of Hb variants and the ethnic origin of a given population, every individual laboratory must establish and validate its own assay method. In managing diabetic patients, knowledge of hemoglobinopathies influencing HbA1c determination methods is essential because hemoglobin variants could cause mismanagement of diabetes resulting from false HbA1c determinations.

Biomarkers↗
PubMed1999

Anti-cardiolipin antibodies in patients with inflammatory bowel disease.

Elevated levels of anti-cardiolipin antibodies are associated with an increased risk for venous and arterial thrombosis. In patients with inflammatory bowel disease thrombosis is a well known complication. We determined the prevalence of elevated anti-cardiolipin antibodies in 136 patients with inflammatory bowel disease compared with 136 healthy controls and analyzed thromboembolic complications in patients with increased anti-cardiolipin antibody levels. Anti-cardiolipin antibody titers were significantly elevated in patients with Crohn's disease (5.7 units/ml) and ulcerative colitis (5.3 units/ml) compared to the control group (2.5 units/ml). We found no correlation between disease activity and anti-cardiolipin antibody levels. Seven patients had deep venous thrombosis in their history, in three of them this was complicated by pulmonary embolism. In only two of the seven patients with deep venous thrombosis were anti-cardiolipin antibody levels increased. In conclusion, anti-cardiolipin antibody titers were significantly increased in patients with inflammatory bowel disease. Elevated anti-cardiolipin antibody levels appear to play no role in the pathogenesis of thromboembolic events in patients with inflammatory bowel disease.

Adult↗
PubMed1999

Effects of intensified lifestyle modification on the need for further revascularization after coronary angioplasty.

BACKGROUND: In patients with coronary artery disease (CAD), a rate of restenosis as high as 50% is observed after percutaneous transluminal coronary angioplasty (PTCA). Frequently, this results in further revascularization procedures. Lifestyle intervention has been shown to slow the progression of CAD and to reduce cardiovascular events after myocardial infarction. However, no information exists whether such treatment influences the rate of restenosis in patients with CAD. The present study was performed to investigate the effects of an intensified lifestyle intervention on the need for further revascularization procedures in patients with established CAD after successful PTCA. DESIGN: A total of 60 patients were included and randomized to either conventional treatment by cardiologists and general practitioners or additional intensified lifestyle intervention in a diabetes and metabolism outpatient clinic for 12 months. The mean observation time after successful PTCA was 26 months. The primary outcome variable was the need for further revascularization procedures because of clinical restenosis. Secondary outcome variables were lifestyle-related measures. RESULTS: Intervention resulted in a reduction in body weight and blood pressure, and in increased physical activity. Furthermore, nutritional habits were changed towards less fat intake, and body composition changed towards a higher proportion of fat-free mass. The need for further revascularization procedures was reduced from a total of 14 out of 32 in the conventionally treated group to 3 out of 28 in the intervention group. This resulted in an event-free survival probability of 0.89 in the intervention group and 0.57 in the control group (P = 0.0055, log rank) with a resulting relative risk of 0.26 (95% CI 0.09-0.74). CONCLUSION: In conclusion, our data strongly suggest that intensified lifestyle modification is able to reduce the need for further revascularization procedures after PTCA in patients with CAD.

Angina Pectoris↗
PubMed1999

Bone scintigraphy and magnetic resonance imaging in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is an acute systemic inflammatory disorder of unknown origin. We report a patient whose AOSD presented with the commonly accepted diagnostic clinical signs and laboratory parameters. The painful joints distinctly demonstrated increased uptake of 99mTc-methylene diphosphonate in scintigraphy and areas of increased gadolinium-enhanced signal in MRI. Biopsies indicated bone marrow edema. AOSD in association with bone marrow edema had not been previously demonstrated. AOSD is often diagnosed after a considerable delay, bone scintigraphy, and magnetic resonance imaging may offer new imaging techniques for early diagnosis and successful therapy in follow-up examinations.

Adult↗
PubMed1999

Relation of serial measurements of plasma-soluble intercellular adhesion molecule-1 to severity of acute pancreatitis.

OBJECTIVE: Acute pancreatitis remains a clinical challenge because it is difficult to predict whether, in a given patient, the disease will be mild or will run a severe course with a possibly fatal outcome. The aim of this study was to investigate whether circulating soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of leukocyte activation is related to the severity of the disease. METHODS: The study included 29 consecutive adults admitted with acute pancreatitis. Plasma sICAM-1 levels were measured serially over a period of 6 days, and values and time courses were correlated with clinical severity. RESULTS: Our patients fell into four groups on the basis of the following measurements: 1) Decreasing sICAM- levels with maximal values of 446 +/- 90 ng/ml (mean +/- SEM) slightly above the upper limit of normal were associated with uncomplicated mild disease in seven patients. 2) In nine patients with sICAM-1 concentrations reaching a peak of 743 +/- 121 ng/ml after 3 days, severe pancreatitis was present in 11% and pancreatic necrosis occurred in 33%. 3) A second increase of sICAM-1 (maximal level: 993 +/- 169 ng/ml) after an initial decrease (relapsing pattern, 7 patients) was associated with a severe course of disease in 71% including pancreatic necrosis in 43% and nosocomial pneumonia in 42%. 4) A rapid increase of sICAM-1 reaching highest maximal values of 1738 +/- 104 ng/ml (p < 0.0001) indicated fulminant pancreatic necrosis and a fatal outcome in six patients. CONCLUSIONS: Serial plasma sICAM-1 levels in patients with acute pancreatitis within the first 6 days after admission fall into four different groups of severity according to the shape of the curves. This suggests that the time course of elevated plasma sICAM-1 concentrations reflects the risk of developing necrosis and clinical complications in acute pancreatitis.

Acute Disease↗
PubMed1998

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Antidotes↗
PubMed1998

Mechanisms and management of antibiotic-associated diarrhea.

Only 10%-20% of all cases of antibiotic-associated diarrhea (AAD) are caused by infection with Clostridium difficile. Other infectious organisms causing AAD include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species, and Salmonella species. Most of the clinically mild AAD cases are due to functional disturbances of intestinal carbohydrate or bile acid metabolism, to allergic and toxic effects of antibiotics on intestinal mucosa, or to pharmacological effects on motility. Saccharomyces boulardii and Enterococcus SF68 can reduce the risk of developing AAD. Patients receiving antibiotic treatment should avoid food containing high amounts of poorly absorbable carbohydrates. Mild cases of AAD that may or may not be caused by C. difficile can be resolved by discontinuation of antibiotic therapy and by dietary carbohydrate reduction. Only severe AAD caused by C. difficile requires specific antibiotic treatment.

Animals↗
PubMed1998

Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain.

BACKGROUND: Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments. AIM: To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo. METHOD: Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) micrograms/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker. RESULTS: At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 micrograms/ml and the subject receiving 50 micrograms/ml experienced crampy abdominal pain. CONCLUSION: The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.

Adult↗
PubMed1998

Validation of home blood glucose meters with respect to clinical and analytical approaches.

OBJECTIVE: To evaluate the clinical and analytical accuracy of home blood glucose meters. RESEARCH DESIGN AND METHODS: Six blood glucose meters--Reflolux S (Boehringer Mannheim, Mannheim, Germany), One Touch II (LifeScan, Milpitas, CA), Glucocard Memory (Menarini, Florence, Italy), Precision QID (Medisense, Cambridge, U.K.), HaemoCue (HaemoCue, Angelholm, Sweden), and Accutrend alpha (Boehringer Mannheim, Mannheim, Germany)--were compared with a reference method (Beckman Glucose Analyzer II) under controlled conditions (glucose clamp technique). Validation of the blood glucose meters was accomplished by clinically oriented approaches (error grid analysis), statistical approaches (variance components analysis), and by the criteria of the American Diabetes Association (ADA), which recommend a target variability of < 5%. RESULTS: A total of 1,794 blood glucose monitor readings and 299 reference values ranging from 2.2 to 18.2 mmol/l were analyzed (705 readings < 3.89 mmol/l, 839 readings between 3.89 and 9.99 mmol/l, and 250 readings > 9.99 mmol/l). According to error grid analysis, only Reflolux S and Glucocard M had 100% of estimations within the clinically acceptable zones A and B. Assessment of analytical accuracy revealed substantial differences between the glucose meters after separation of the data into defined glycemic ranges. None of the devices met the ADA criteria. CONCLUSIONS: To evaluate accuracy of blood glucose meters, error grid analysis, as well as statistical models, are helpful means and should be performed together. Analytical performance of currently available home blood glucose meters differs substantially within defined glycemic ranges.

Blood Glucose Self-Monitoring↗
PubMed1998

Short-term efficacy and long-term outcome of cyclosporine treatment in patients with severe ulcerative colitis.

Cyclosporine A (CyA) has been recommended for the treatment of severe steroid-resistant ulcerative colitis, however, long-term results are scarce. We prospectively followed a treatment plan in 14 patients with severe ulcerative colitis receiving intravenous CyA after failure to respond to at least eight days of standard therapy with prednisolone (1-1.5 mg/kg/day). CyA was delivered in a daily dose of 5 mg/kg i.v. for a mean of 14 days (range 7-28) in addition to ongoing medical therapy. CyA whole blood levels were monitored by HPLC and maintained between 100 ng/ml and 400 ng/ml. Responders were switched to oral CyA (5-7.5 mg/kg/day) for a mean of two months, and steroids were gradually tapered. Eleven patients (79%) initially responded to i.v. CyA, three patients failed to respond and underwent urgent colectomy. Time until response averaged seven days (range 3-13). Four of the eleven responders underwent colectomy because of severe relapse after one, eleven, twelve and 13 months of follow-up. The remaining seven patients were followed for a median of 48 months. During the first year of follow-up three out of seven had a severe relapse and responded to steroids (two patients) or to a further course of i.v. CyA (one patient). During CyA therapy one patient developed staphylococcal sepsis, other adverse events were mild and reversible. The results confirm that CyA is effective in severe steroid-refractory ulcerative colitis. Severe relapse and colectomy are uncommon after the first year of follow-up and the colon preserving effect of CyA can be maintained in up to 50% of patients over a period of four years.

Adult↗
PubMed1997

End-stage renal failure from mushroom poisoning with Cortinarius orellanus: report of four cases and review of the literature.

Mushrooms of the ubiquitous Cortinarius species (Cs) contain nephrotoxins that can cause acute and chronic renal failure by an unknown pathomechanism. Typical is a long symptom-free interval before the onset of clinical disease. A causal form of therapy is not known. Early hemodialysis can improve the prognosis of this potentially life-threatening condition. Diagnosis of Cs poisoning can be made by detecting the responsible toxin--orellanine--in plasma or renal tissue by fluorimetry after thin-layer chromatography or by identifying the spores of left-over mushrooms as Cs. Renal histology shows nonspecific changes such as tubular dilatation and flattening of the epithelium and signs of interstitial edema followed by interstitial fibrosis. We present four cases of Cs poisoning with different outcomes and a review of the literature.

2,2'-Dipyridyl↗