Does liver biopsy overestimate liver iron concentration?
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Benzoates↗
Biomedical subjects
Peter Nielsen
Publications and source records attributed to Peter Nielsen.
Does liver biopsy overestimate liver iron concentration?
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Biopsy↗
Temporary esophageal stenting allows healing of esophageal perforations following atrial fibrillation ablation procedures.
BACKGROUND: Left atrial catheter ablation (LACA) has emerged as a successful method to eliminate atrial fibrillation (AF). Recent reports have described atrio-esophageal fistulas, often resulting in death, from this procedure. Temporary esophageal stenting is an established therapy for malignant esophageal disease. We describe the first case of successful temporary esophageal stenting for an esophageal perforation following LACA. CASE: A 48-year-old man with symptomatic drug refractory lone AF underwent an uneventful LACA. Fifty-nine ablations with an 8-mm tip ablation catheter (30 seconds, 70 Watts, 55 degrees C), as guided by 3-D NavX mapping, were performed in the left atrium to isolate the pulmonary veins as well as a left atrial flutter and roof ablation line. In addition, complex atrial electrograms in AF and sites of vagal innervation were ablated. Two weeks later, he presented with sub-sternal chest pain, fever, and dysphagia. A chest CT showed a 3-mm esophageal perforation at the level of the left atrium with mediastinal soiling and no pericardial effusion. An urgent upper endoscopy with placement of a PolyFlex removable esophageal stent to seal off the esophago-mediastinal fistula was performed. After 3 weeks of i.v. antibiotics, naso-jejunal tube feedings, and esophageal stenting, the perforation resolved and the stent was removed. Over 18 months of follow-up, there have been no other complications, and he has returned to a physically active life and remains free from AF on previously ineffective anti-arrhythmic drugs. CONCLUSION: Early diagnosis of esophageal perforations following LACA may allow temporary esophageal stenting with successful esophageal healing. Prompt chest CT scans with oral and i.v. contrast should be considered in any patient with sub-sternal chest pain or dysphagia following LACA.
Atrial Fibrillation↗
Far forward gynecologic care of the female soldier.
OBJECTIVE: To evaluate the value, unit cost and medical effectiveness of providing specialized obstetric and gynecologic care far forward, at echelon III, the combat support hospital (CSH), in the operating theater of Afghanistan during Operation Enduring Freedom (OEF), rotation 5. STUDY DESIGN: Between April 2004 and September 2004, records were reviewed from the outpatient gynecology clinic at Bagram Air Field (BAF), in Afghanistan, through an approved protocol request. Cohort analysis was performed on all gynecologic patients. Significant differences in distribution of clinical factors were determined by Student's t test. RESULTS: A total of 62 cases were extracted for analysis over the 6-month period. Fifty-seven total patients were seen at echelon III, the CSH at BAF, while 5 were sent to level IV or V echelon care in Landstuhl, Germany. The average distance traveled for the patients coming to BAF was 158 km, while those sent to Germany averaged 5,204 km. The mean travel time in days was significantly lower among patients seen at BAF, 0.5 versus 7 days for patients sent to Germany. The time to appointment was also significantly lower among those patients seen at BAF: 0.04 versus 13 days for patients sent to Germany. CONCLUSION: We devised and implemented the concept of far forward specialized gynecologic care for women participating in OEF. This substantially decreased the woman-hours lost by their individual units. The far forward availability of gynecologic care and the supplies to evaluate and treat abnormal Pap smears should be considered by all military services in their plans for providing health care for the modern female soldier.
Afghanistan↗
Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation.
Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.
Ascorbic Acid↗
Nuclear iron deposits in hepatocytes of iron-loaded HFE-knock-out mice: a morphometric and immunocytochemical analysis.
Nuclear deposits of stainable iron in hepatocytes are a sign of liver iron overload in mice. Animals with no, partial or total knock-out of the HFE alleles, the deletion of which is responsible for hereditary haemochromatosis, were given different forms of dietary iron to measure nuclear iron deposits which were then related to cytoplasmic iron load. Wild type and heterozygous HFE-knock-out mice kept for 52 weeks on a standard diet showed no such deposits. These were, however, demonstrated in low numbers and with small diameters in homozygous HFE-knock-out mice kept on this diet. Nuclear iron deposits were most abundant in all type of mice fed carbonyl iron (2.5% w/w) for 52 weeks almost irrespective of their genetic background. The diameter of these deposits increased with the genetically conditioned extent of hepatocellular iron overload. Mice that were fed a diet containing TMH-ferrocene for 4 weeks showed amounts of hepatic iron that were comparable to those in the carbonyl iron-fed group but nuclear deposits were small and present in only 0.3% of the hepatocytes. While surrounding karyoplasm was immunostained for H- and L-ferritin, the nuclear iron deposits were not. As the nuclear iron deposits corresponded electron microscopically to aggregated ferritin molecules, they represent a non-immunoreactive form of presumably denatured ferritin.
Animals↗
Assessment of resident surgical skills: is testing feasible?
OBJECTIVE: We have previously shown that in a single residency program objective structured assessment of technical skills (OSATS) is a reliable and valid method of assessing surgical competency. Our goal was to establish feasibility of this evaluation instrument when administered at multiple residency programs throughout the US, and assess the impact of a laboratory-based surgical curriculum on results. STUDY DESIGN: An OSATS exam was administered to 116 residents from 5 residency programs. One of the residency programs had participated in a comprehensive surgical curriculum over a 4-year period of time. The exam consisted of 3 open and 3 laparoscopic tasks. Residents were graded by both a blinded and unblinded examiner with task-specific checklist, global rating scale, pass/fail assessment, and tasks were timed. All tasks were performed on life-like models. RESULTS: Examinations were successfully completed at all sites. Each exam required 90 minutes of resident time. Reliability indices calculated with Cronbach's alpha were .97 for overall global rating and .95 for checklists. Interrater reliability between blinded and unblinded examiners ranged from .71 to .97 for individual tasks and was .95 overall. Assessment of construct validity (the ability to distinguish among residency levels) found significant differences among the residents for both blinded and unblinded examiners for all evaluation outcomes except time. For the test overall, the global rating scale showed significant differences among all 4 residency levels. The checklist showed significant differences at three levels (PGY3-4 >PGY2 >PGY1). Approximate cost for replaceable items was 40 US dollars to 150 per resident depending on which tasks were chosen. Comparison of scores between residents who received a laboratory-based curriculum and those who did not revealed significantly higher scores and shorter time to complete tasks for the group who received additional training. CONCLUSION: Large-scale testing has confirmed that OSATS is an objective, reliable, and valid method to assess surgical skills, and can easily be administered in most residency programs. A laboratory-based surgical curriculum improved test results and reduced time to complete tasks.
Clinical Competence↗
A new curriculum for hysteroscopy training as demonstrated by an objective structured assessment of technical skills (OSATS).
OBJECTIVE: The purpose of this study was to develop an effective curriculum to teach hysteroscopy, as well as to develop an objective assessment instrument (OSATS). STUDY DESIGN: All 24 residents in our training program attended a 3-hour hysteroscopy curriculum in each of 3 years. Each year after the curriculum, an OSATS was administered consisting of an assembly and operative task. Each task was evaluated with a task-specific checklist and a previously validated global assessment form. Twenty-four residents from an outside institution served as controls. All residents were examined by blinded and unblinded examiners. RESULTS: The reliability coefficient was .7857 for the checklist and .9763 for the global scale. Interrater reliability for the checklist was .7478 and ranged from .4222 to .9329 for the global instruments. Evaluation of construct validity revealed that the junior residents at both locations did significantly worse on the checklist and global scale than the senior residents for all 3 years of the study (P < .001). Those residents provided the curriculum did significantly better on both the checklist and the global scale than the resident controls with a mean of 45% versus 63% for the checklist and 18.3 versus 24.9 for the global score. (P = .001 checklist, P = .007 global scale). CONCLUSION: This curriculum is an effective way to impart knowledge and skill in the assembly and use of the operative hysteroscope. The checklist developed for this OSATS has excellent reliability and construct validity.
Clinical Competence↗
Bioavailability of oral iron drugs as judged by a 59Fe-whole-body counting technique in patients with iron deficiency anaemia. Therapeutic efficacy of iron(II)-glycine sulfate.
The bioavailability of the oral iron compound iron(II)-glycine sulfate (ferro sanol duodenal, FSD, 1 x 100 mg Fe/d) was studied in 56 patients with iron deficiency anaemia using a 59Fe-labelling technique and 59Fe-whole-body counting. This technique measures the individual iron loss and allows in patients with substantial blood loss under iron medication a reliable information on the bioavailability of the drug. In all patients, the increased loss of iron (mean 5.8 +/- 4.4 mg/d) was clearly compensated by the iron utilisation (mean: 11.1 +/- 5.6 mg/d) from a daily dosage of 100 mg iron from FSD. A significant increase in the haemoglobin concentration was observed within the monitored treatment period of 6-10 weeks (mean Hb increase from 10.7 +/- 1.7 to 12.1 +/- 1.8 g/dl). FSD has therefore documented a bioavailability of at least 11% from a single daily dose of 100 mg Fe and was effective in the treatment of the anaemia in almost all patients under study.
Adult↗
Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry.
In patients with thalassemia, the assessment of liver iron concentration (LIC) can be used to initiate chelation treatment with desferrioxamine (DFO), deferiprone (DFP), or novel chelators (deferasirox); to adjust chelation dose according to the actual blood transfusion rate; and to monitor chelation efficacy. The results from measurements by SQUID biomagnetic liver susceptometry in the LIC range 17-11,500 microg/g of liver in about 1000 patients were used to derive nonstandard parameters, which may be useful in the treatment monitoring of patients with thalassemia. From these measurements, including liver volumes, the documented chelation dose rates, and the blood transfusion rates, the chelator index (equivalent Therapeutical Index), the total body iron elimination rate, and the molar efficacy were calculated. Chelator indices (CIs) ranged from 0.1 to 11.7 mmol/d/g of Fe for DFO, with a threshold of CI greater than 1.2 mmol/d/g of Fe indicating DFO toxicity. For DFP, CI ranged from 0.1 to 23.2 mmol/d/g of Fe. In long-term studies (2 and 4 years), mean molar efficacies of DFO and DFP were found to be quite stable with 17.6 +/- 4.8% and 4.9 +/- 1.4%, respectively. Currently, specific chelation dose is based upon body weight. Because liver iron measurements by biosusceptometry are now regularly available in Europe and America, as well as quantitative MRI worldwide, these methods may be used to adjust chelation treatment regimens to body iron stores.
Algorithms↗
Non-transferrin-bound iron during blood transfusion cycles in beta-thalassemia major.
Serum non-transferrin-bound iron (NTBI) levels assessed at arbitrary time points during transfusion cycles may not be representative if NTBI is undergoing significant changes during transfusion cycles. In 15 patients with beta-thalassemia major (age: 21 +/- 6 years, liver iron concentration: 2200 +/- 1200 microg/g-liver), NTBI and other hematologic parameters (transferrin saturation, transferrin receptor) were measured weekly. The largest variation of NTBI levels between individual patients was observed at midcycle. For long-term monitoring of NTBI levels, a particular time point relative to the last blood transfusion should be selected for blood drawing.
Adolescent↗
Low dose-ethanol modulates toxic effect of iron-overloading in the liver.
UNLABELLED: The oxidant properties of iron-overload and simultaneous ethanol consumption have received much interest, due to evidence reporting from hereditary hemochromatosis (HC). The full form of this disease is often associated with chronic alcoholism. An additive effect of toxicity of iron and ethanol was assumed. In this study, we examined nutritively iron-loaded Wistar rats (n = 59) (TMH-Ferrocene) additionally fed with ethanol up to 8% in drinking water for 36 wk. METHODS: By reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole and retinol in serum and liver homogenates as well as transaminases in the serum. Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron concentration in the liver was measured with the Bathophenanthrolin-method. Liver histology was performed to investigate the iron deposits and the organ damage (H.E., Azan and Berlin-blue-stainings). RESULTS: 1. Vitamin C: A linear decrease of the concentration of vitamin C in serum and liver was found independent of alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin A: Elevated levels in serum but strongly decreasing levels in liver could be measured. 4. HISTOLOGY: All iron-fed animals showed massive deposits of iron in the liver. Iron diet caused liver cirrhosis, while an additional administration of ethanol could prevent this. 5. Lipid peroxidation increased in animals fed ethanol and iron, but was significantly lower in animals only receiving an iron diet. CONCLUSION: Evidence indicates that the additional exposition to ethanol in iron-loaded animals could modulate the organ damage and oxidative stress. The biochemical findings are positively correlated to the histology.
Alanine Transaminase↗
Targeting structured nucleic acids with antisense agents.
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Animals↗
Monitoring long-term efficacy of iron chelation therapy by deferiprone and desferrioxamine in patients with beta-thalassaemia major: application of SQUID biomagnetic liver susceptometry.
In this non-randomized prospective study, liver and spleen iron concentrations were monitored annually over a 4-year period by non-invasive Superconducting Quantum Interference Device biomagnetometry in 54 beta-thalassaemia major patients (age, 7-22 years) receiving treatment with deferiprone (75 mg/kg/d). Median liver iron concentrations increased significantly from 1456 to 2029 and 2449 microg/g(liver) at baseline, after 2.0 and 3.2 years respectively. Another group of 51 thalassaemic patients (aged 4-34 years) who received desferrioxamine s.c. for 1.9 years increased their liver iron concentration from 1076 to 1260 microg/g(liver). Taking into account the increase of the daily iron input from transfusions of 3.6 mg/d, caused by weight gain in 67% of the patients treated with deferiprone, a larger total body iron elimination rate was achieved after 2 years than at baseline. A negative ferritin change was observed in 51% of the patients. In 15 non-splenectomized patients, liver iron significantly increased from 1260 to 1937 microg/g(liver) (P < 0.01), but serum ferritin remained stable at 2100 microg/l, as did the spleen iron concentration at 1200 microg/g(spleen). A two-compartment model may predict an average chelation efficacy for desferrioxamine and deferiprone, with a saturation effect of the latter, for a certain chelation and transfusion regimen by a single liver iron quantification.
Adolescent↗
Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases.
The treatment of iron overload by s.c. desferrioxamine (DFO) was studied in three patients with hereditary haemochromatosis in which phlebotomy treatment was not, or transiently not, possible because of their serious clinical condition or the lack of appropriate peripheral veins. Repeated non-invasive liver iron concentration measurements by superconducting quantum interference device biosusceptometry showed that DFO treatment (2 g/d for 9-11 months) was as effective (liver iron elimination rate: 12 mg/d) as normal phlebotomy treatment (5.9 or 14.3 mg/d respectively) with weekly 500-ml blood removals. This demonstrates that DFO is an effective alternative therapy for haemochromatosis when phlebotomy is not possible.
Deferoxamine↗
The influence of deferiprone (L1) and deferoxamine on iron and essential element tissue level and parameters of oxidative status in dietary iron-loaded mice.
The seven week feeding of a diet enriched with 0.5% TMH-ferrocene to male mice was used in this study to produce an iron-overload model in experimental animals for evaluating the effect of deferoxamine (DFO) and deferiprone (L1) on tissue-stored iron, induced lipid peroxidation (LP) and parameters of oxidative status. The iron concentration in the liver reached 600% of the level in control animals. The administration of seven doses of deferoxamine (DFO) i.p. and deferiprone (L1) p.o. (0.72 mmol/kg b.w., every 48 h) during 9th and 10th week significantly decreased the liver, kidneys and heart iron level in both iron-loaded and control mice. The DFO and L1 treatment also equally attenuated lipid peroxidation and increased the GSH level in the liver of iron loaded mice. The glutathione peroxidase (GSH-Px) activity and catalase activity were not affected by iron loading, however, both DFO and L1 caused a decrease of GSH-Px activity.
Animals↗
Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis.
In the HFE-gene era, precise diagnostic parameters remain important to characterize individual iron stores, because the indication for therapy and prognosis are mainly related to the extent of iron loading. The frequently used serum ferritin interferes with non-iron related factors such as inflammation and may produce falsely positive values. We used a SQUID-biosusceptometer in a large series of patients (n = 679) to measure liver iron concentration in the differential diagnosis and therapy control of hereditary hemochromatosis (SQUID = superconducting quantum interference device). This truly non-invasive technique is sensitive, reliable, fast (online results), and also cost-effective when compared to invasive liver biopsy. Recently, ferritin iron content was propagated as a better parameter than ferritin protein. However, we found a poor correlation between ferritin iron and individual liver iron concentrations in patients with iron overload. Ferritin iron saturation varied in a range between 3 and 10%, independent from liver iron concentration. No differences were found between patients with hemochromatosis and secondary iron overload disease. Only patients with liver cell damage had increased ferritin iron saturations. In conclusion the diagnostic values of serum ferritin protein and iron to assess iron overload are limited.
Ferritins↗
Evaluation of the use of liquid dishwashing compounds to control bacteria in kitchen sponges.
A test procedure for evaluating the effect of adding commercial liquid hand dishwashing detergents to kitchen sponges to control microbial growth is described. Claims for this type of application are being made on dishwashing detergents throughout the world. In this evaluation, commercially available kitchen sponges were stripped of antimicrobial compounds. Sponges were then inoculated with a pool of 7 microorganisms which consisted of gram positives, gram negatives, and yeast. Inoculated sponges were treated with the detergent as recommended by the manufacturer and allowed to incubate for 16 h at ambient temperature. Surviving microorganisms were then quantitated using either the spiral or pour plate method. Tests were run using both clean sponges and sponges soiled with 0.5% nonfat dry milk (NFDM). Untreated sponges showed stasis or slightly increased bacterial populations after the incubation period in the absence of NFDM. Significant increases of up to 3 log cfu/mL were observed for untreated sponges when soiled with NFDM. Statistically significant reductions were observed for clean sponges (99.8-99.9998%) and sponges soiled with NFDM (87.6-99.9%) when detergents making "antibacterial sponge" claims were added to the inoculated sponges. Statistically significant differences between detergents making "antibacterial sponge" claims were also observed.
Bacteria↗