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Biomedical subjects

J Berger

Publications and source records attributed to J Berger.

At least 163 records · Page 9Linked to original sources

Changing bacterial ecology during a five-year period of selective intestinal decontamination.

The development of bacterial resistance during selective decontamination of the digestive tract (SDD) is controversial. We studied effects on bacterial resistance one year before and during a randomized, placebo-controlled trial of SDD in a surgical intensive care unit. We randomized patients within two different topical regimens (PTA, PCA) or placebo, administered four-times daily to both the oropharynx and gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg b.d.) for four days. Both SDD regimens successfully reduced aerobic Gram-negative intestinal colonization. There was no increase in resistance of Enterobacteriaceae or Pseudomonas aeruginosa. Acinetobacter calcoaceticus developed multi-resistance over one year, but differences between groups were not significant. We detected a shift towards Gram-positive organisms. Oxacillin-resistant Staphylococcus aureus increased in concert with ciprofloxacin resistance, from 17 to 80.7%, and frequencies of resistance were significantly higher in SDD patients (P < 0.001). Resistance of coagulase-negative staphylococci (CNS) to oxacillin increased initially (25 to 66.9%), but values returned to baseline in controls. Ciprofloxacin resistance in CNS remained higher (P < 0.001) in SDD-treated patients (52.5 vs. 23.3%). The incidence of late respiratory tract infections was unaltered by the prophylactic regimen (SDD 35.2%; Placebo 41.2%; n.s.). We cannot recommend SDD as a prophylactic tool in critically ill patients.

Adult↗

Stenting of nonacute total coronary occlusions: predictors of late angiographic outcome.

OBJECTIVES: This study was designed to determine and assess factors predictive of the intermediate-term outcome of stenting of nonacute total coronary occlusions. BACKGROUND: Balloon angioplasty of recanalized coronary occlusions is associated with a combined restenosis/reocclusion rate of up to 65%. Adjunctive stenting holds the potential to reduce this rate significantly. However, variables affecting the late angiographic outcome of coronary stenting in the setting of a total occlusion have not been elucidated sufficiently. METHODS: Coronary stenting was performed in 143 consecutive patients with a nonacute total occlusion; 120 of these patients (84%), with a total of 121 occlusions, underwent repeat angiography within 6 months and comprised the study group. High pressure stent implantation aimed to cover the site of the occlusion as well as adjacent diameter stenoses > or = 70% and all possibly induced dissections. Pertinent angiographic and procedural variables obtained at the time of the intervention were entered into a multivariate logistic regression analysis model to assess their influence on the angiographic outcome at follow-up. RESULTS: Mean preinterventional reference lumen diameter for the 121 vessels was 2.99 +/- 0.53 mm (mean +/- SD); occlusion length ranged from 4 to 44 mm (median of 7.7). After balloon angioplasty, dissections were found in 80% of patients. Lesions were covered with stents a median of 16 mm in length (range 8 to 53). The minimal lumen diameter (MLD) achieved after stenting was 2.89 +/- 0.48 mm. After a median follow-up period of 4.5 months, mean MLD was assessed at 1.91 +/- 0.90 mm, corresponding to a loss index of 0.34 +/- 0.31. There were 27 vessels with a nonocclusive restenosis > or = 50% and 8 with a reocclusion, for a combined restenosis/reocclusion rate of 29%. Factors found to adversely influence angiographic outcome were a post-stenting MLD < or = 2.54 mm, a stented vessel segment length > 16 mm, a balloon/vessel diameter ratio for final stent expansion < or = 1.00 and the presence of a dissection after balloon angioplasty. CONCLUSIONS: Compared with previous reports on stand-alone balloon angioplasty, stenting of nonacute total coronary occlusions lowers the 6-month restenosis/reocclusion rate to approximately 30%. The late procedural outcome is independently and statistically significantly influenced by the MLD after stenting, the length of the stented vessel segment, the balloon/vessel diameter ratio for final stent expansion and the incidence of dissections after balloon angioplasty.

Analysis of Variance↗

Effects of protraction mechanics on the midface.

Forty patients with Class III maxillary deficiencies were each treated with a bonded maxillary palatal expansion appliance followed by protraction. Nineteen of the 40 patients were retained with a Frankel III appliance. This group was compared with 24 Class I patients treated solely with bonded expansion appliance mechanotherapy. To determine at which level protraction mechanics affects the maxilla, the Walker's analysis and other cephalometric measurements were used. The protraction group showed significant increases (p <.05) in the following measurements: ANB angle, Wits, A perpendicular to nasion and in sella to A point. Anterior molar movement, without changes in posterior nasal spine or upper incisor to SN, was evident (p <.05). Favorable change in the facial profile was noted. There were no changes in the angles between sella-nasion and its relationship with the Frankfurt, occlusal, palatal, and mandibular planes. Walker's analysis showed no change in the position of orbitale. The control group did not demonstrate any significant changes in the position of the maxillary complex as a result of expansion mechanics. The retention group maintained the position of the maxilla postprotraction. Facial contour was maintained and other profile related variables improved.

Analysis of Variance↗

Activation-dependent expression of the insulin-like growth factor binding protein-2 in human lymphocytes.

The expression of the insulin-like growth factor binding protein-2 (IGFBP-2) was assayed in mononuclear cells originating from different organs of the immune system. All mononuclear cells studied did express IGFBP-2, but the expression level was found to be dependent on the cell type and origin of the cell. T cells showed a higher expression of IGFBP-2 mRNA than did B cells, and CD34+ stem cells expressed IGFBP-2 mRNA at a high level. Expression was highest in bone marrow and thymus. Stimulation of peripheral mononuclear cells resulted in a marked increase of IGFBP-2 mRNA and also intracellular IGFBP-2, as analysed by fluorescence staining. This increase parallels the increase of other known T-cell activation markers. Furthermore, the increase of intracellular IGFBP-2 seems to precede T-cell blast formation and all T cells in active phases of the cell cycle have high levels of IGFBP-2. Our results provide a basis for further investigations on the contribution of the IGF-system to the regulation of T-cell proliferation and differentiation. IGFBP-2, in particular, may have an important influence in the regulation of T-cell activation and proliferation.

Cell Culture Techniques↗

Perioperative ventricular dysrhythmias in patients with structural heart disease undergoing noncardiac surgery.

UNLABELLED: Noncardiac surgical patients with preoperative ventricular dysrhythmias and structural heart disease may be at increased risk of adverse cardiac outcome. We evaluated how anesthesia and surgery affect the course of ventricular dysrhythmias (premature ventricular beats [PVB] and repetitive forms of ventricular beats [RFVB]: couplets and nonsustained ventricular tachycardia) noted preoperatively in patients with structural heart disease and whether the frequency of ventricular dysrhythmias affects cardiac outcome. In a prospective study, 70 patients scheduled for noncardiac surgery with structural heart disease and RFVB on preoperative Holter electrocardiogram were continuously monitored intraoperatively and for 3 days postoperatively. Holter tracings were analyzed for rhythm, medians of total PVB and RFVB per hour. Preoperative RFVB recurred intraoperatively in 35% and postoperatively in 87% of patients. There was a significant intra- and postoperative decrease of total PVB per hour (P < 0.05) and RFVB per hour (P < 0.01). Frequency of ventricular dysrhythmias in the five patients suffering adverse outcome (unstable angina, n = 1; congestive heart failure, n = 4) did not significantly differ from those with good outcome. We conclude that in noncardiac surgical patients with structural heart disease and RFVB, the frequency of ventricular dysrhythmias is not associated with adverse cardiac outcome. IMPLICATIONS: Using continuous electrocardiogram monitoring, we investigated whether the frequency of perioperative ventricular dysrhythmias independently affects outcome in patients with structural heart disease undergoing noncardiac surgery. The incidence of perioperative dysrhythmia in patients with an adverse outcome (8%) did not differ from those with a good outcome.

Adult↗

A new high-resolution esophageal electrocardiography recording technique: an experimental approach for the detection of myocardial ischemia.

UNLABELLED: Criteria for ischemic changes in the esophageal electrocardiograph (E-ECG) have not been standardized and validated. The main goal of this study was to evaluate the experimental esophageal recording of myocardial ischemia and to assess the association between ST segment alternans in the E-ECG and ischemia. Experiments were performed on 18 anesthetized sheep with occlusion of a branch of the left anterior descending artery. The bipolar signals were recorded via an esophageal lead containing three chloridized silver electrodes. Electrical signals were amplified in a self-designed, battery-supported preamplifier (gain 1000, frequency range 0.01-2000 Hz, common mode rejection 140 dB, signal noise 5-7 microV p-p), then sent to a digital oscilloscope for display and to a pulse code-modulated recorder. Surface electrocardiography (S-ECG) data were also recorded. Ischemia E-ECG revealed homogenous ST segments without any beat-to-beat alternans. Two minutes after occlusion, 14 of 15 sheep (93%) showed repetitive beat-to-beat fluctuations within the ST segment on the E-ECG. Of the 15 sheep, 7 (47%) showed ischemia in the S-ECG (P < 0.01). For calculation of the dynamic changes in the ST segment in the E-ECG, the difference in the amplitudes of the ST segment of five successive beats to the next beat, performed for 200 consecutive beats, was calculated. The central tendency of the sum of these values before versus during ischemia was 2000 mV/ms versus 5000 mV/ms (Hodges-Lehmann point estimator) (95% confidence intervals 1700/2500 versus 3350/9250 [lower limit/upper limit]). The authors have established a close temporal relationship between the magnitude of ST segment alternans recorded via E-ECG and myocardial ischemia. IMPLICATIONS: The study presents the use of an esophageal electrocardiograph for detection of progressive changes of myocardial ischemia and infarction. During acute myocardial ischemia and infarction in sheep, the esophageal electrocardiograph has visually apparent ST alternans of amplitude in the millivolt range, in part due to a special amplifier (0.01-2000 Hz). This is therefore one very promising technique for better evaluation of electrocardiographic changes of ischemia.

Animals↗

Age-dependent differences in the prevalence of allergic rhinitis and atopic sensitization between an eastern and a western German city.

Recent studies have found a higher prevalence of allergic rhinitis and atopic sensitization among adults living in eastern than those living in western Germany. We hypothesize that prevalence rates were similar before Germany was divided and diverged after the division. Because there are no historical data comparing atopic status between the two parts of Germany, we tested this hypothesis by comparing the prevalence of atopy among persons who were born during different decades. As part of the EC Respiratory Health Survey, a respiratory health questionnaire was mailed to a population-based sample of 8363 subjects aged 20-44 years from a city in the former West Germany (Hamburg) and a city in the former East Germany (Erfurt). Of the target population, 6428 (77%) subjects responded. Subsamples of 731 subjects from Erfurt and 1159 subjects from Hamburg participated in medical examinations, including skin prick tests and specific IgE measurements. Prevalence rates of allergic sensitization were similar in Hamburg and Erfurt for those born in the periods 1946-51 and 1952-61, respectively, but differed between Hamburg and Erfurt subjects born in the period 1962-71. After adjustment for several potential predictors, the younger subjects from Hamburg had a higher odds ratio (OR) of sensitization than those Hamburg subjects born before 1952 (skin prick test reactivity: OR 2.06, any specific IgE > 0.35 kU/l: OR 1.61). The younger subjects from Erfurt were not more frequently sensitized than the older subjects (skin prick test reactivity: OR 1.05, any specific IgE > 0.35 kU/l: OR 0.79). No single allergen could be identified as responsible for the observed difference. We conclude that factors related to a "Western lifestyle", which were prevalent in the West German city during the 1960s and 1970s, may be responsible for the higher prevalence of allergic sensitization observed in Hamburg.

Adult↗

DA1-receptor stimulation by fenoldopam in the treatment of postcardiac surgical hypertension.

BACKGROUND: Besides adequate analgesia, sedation and ventilation, postcardiac surgical hypertension has to be treated frequently with vasoactive drugs to avoid possible complications. In this study the hemodynamic effects of the DA1-receptor agonist fenoldopam (F) are compared to those of the Ca-channel antagonist nifedipine (N). METHODS: Postoperatively, 64 CABG-patients with a mean arterial pressure (MAP) of more than 105 mmHg over 10 min were investigated. Patients with compromised ventricular function, insufficient surgical repair, arrhythmia or an ECG unable to detect myocardial ischemia were excluded. The study drugs (initial dosage: F: 0.8; N: 0.3 micrograms.kg-1.min-1) were given continuously via a central venous catheter to reduce and to maintain the MAP between 80 and 95 mmHg. Hemodynamic parameters were determined using thermodilution technique. RESULTS: A significant reduction of the MAP (F: from 121 +/- 11 to 83 +/- 4, N: from 119 +/- 8 to 82 +/- 9 mmHg) and of the calculated systemic vascular resistance (SVR) (F: 2110 +/- 500 to 970 +/- 200, N:1980 +/- 660 to 1020 +/- 300 dyn.s.cm-5) were noted in both groups, whereby in the F group the therapeutic goal could be achieved more quickly with the dosage regimen chosen. As a result, a marked increase of heart rate, cardiac index and stroke volume index could be observed, which was more pronounced due to the initially stronger decrease of SVR with F. There was also a stronger decrease of pulmonary vascular resistance in the F group, but the indices of right ventricular function did not differ between the groups. CONCLUSION: Fenoldopam seems to be an efficient alternative to nifedipine, especially because of its more rapid onset of action.

Antihypertensive Agents↗

alpha-1-Microglobulin: epidemiological indicator for tubular dysfunction induced by cadmium?

OBJECTIVES: To evaluate the suitability of alpha-1-microglobulin as a marker for cadmium induced renal dysfunction. METHODS: alpha-1-Microglobulin was studied in a cross sectional survey in relation to the body burden of cadmium. Concentrations of alpha-1-microglobulin in 24 h urine of 831 people aged 2-87 years were analysed in association with urinary cadmium excretion, cadmium blood concentration, age, sex, occupational and smoking history, and estimated creatinine clearance. Participants came from a population residentially exposed to cadmium and from two control populations matched for socioeconomic status. RESULTS: The excretion of alpha-1-microglobulin/24 h ranged from 0.1 mg to 176.3 mg and 44.4% of samples showed concentrations near the detection limit. Ordinal logistic regression analysis of people of all ages identified a high risk only for males compared with females (odds ratio (OR) 2.14; 95% confidence interval (95% CI) 1.56 to 2.94), age group, and duration of living on contaminated soil (OR 1.03/year; 95% CI 1.02 to 1.04), but not urinary cadmium excretion (OR 1.30; 95% CI 0.96 to 1.77) as significant predictors. For people < or = 50 years of age a weaker effect of sex (OR 1.76; 95% CI 1.13 to 2.73) and age group and an effect of similar magnitude for the duration of soil exposure (OR 1.03; 95% CI 1.01 to 1.04) were found. Also, the urinary cadmium excretion (OR 2.26; 95% CI 1.38 to 3.70) and occupational exposure (OR 1.71; 95% CI 1.03 to 2.83) were found to be significant in this younger age group. The estimated creatinine clearance had no significant impact on the alpha-1-microglobulin excretion. CONCLUSION: alpha-1-Microglobulin is a suitable marker for early tubular changes only for people < or = 50 years. It may not be sufficiently specific for cadmium, and therefore not a suitable surrogate for cadmium exposure in epidemiological studies.

Adolescent↗

Localization of Staphylococcus aureus in infected airways of patients with cystic fibrosis and in a cell culture model of S. aureus adherence.

Staphylococcus aureus causes chronic respiratory tract infections in patients with cystic fibrosis (CF). Using immunofluorescence and scanning and transmission electron microscopy we located S. aureus in lung specimens of three infected CF patients, in a nasal polyp of one CF patient, and in a suspension cell culture system of primary nasal epithelial cells in vitro. Very little of S. aureus was attached to the lung epithelium, whereas abundant S. aureus was detectable in the mucus of obstructed airways. Similarly, S. aureus adhered to components of secreted mucus on primary nasal epithelial cells of CF patients and healthy control subjects, grown as cell balls in vitro (bacteria/cell +/- SD: CF: 21.9 +/- 1.5; controls: 22. 0 +/- 5.8). Mucus depletion of cell balls prior to incubation with S. aureus resulted in a significantly reduced binding (bacteria/cell +/- SD: CF: 4.2 +/- 0.3; P < 0.001; controls: 5.0 +/- 1.3; P < 0. 007). Binding of S. aureus to cell balls from CF patients or control subjects did not differ significantly. When cell balls were treated with human neutrophil elastase, hypersecretion caused removal of S. aureus from cell-associated mucus. The results suggest that S. aureus adheres primarily to mucus components of the respiratory epithelium and that significant differences do not exist in binding of S. aureus to CF or non-CF cells.

Adolescent↗

Learning disabilities with and without attention-deficit hyperactivity disorder: parents' and teachers' perspectives.

Our objective was to delineate the educational and behavioral differences between learning disabled children with and without attention-deficit hyperactivity disorder (ADHD). A restrospective (TROHOC) multimeasure comparative design was employed. Parents' and teachers' questionnaires (ANSER system) pertaining to attention-activity, associated behaviors, and scholastic achievements were compared. Parents' questionnaires failed to distinguish between the two groups. Teachers' questionnaires were significantly more sensitive. Significant correlations between educational achievements and attention-activity and associated behaviors scores among children with learning disabilities were evident, no such correlations were found in the group with learning disability with ADHD. The factor analysis identified different educational and behavioral aggregates with language related difficulties and externalizing behaviors more typically aggregated in the learning disabled group with ADHD and recall deficit and internalizing/neurotic behaviors in the group with learning disability only. ADHD appears to be an associated comorbidity and not necessarily a specific learning deficit. However, children with learning disability with ADHD possibly have a different underlying neurocognitive pattern than their peers with learning disabilities only.

Attention Deficit Disorder with Hyperactivity↗

Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARgamma agonist) action.

Thiazolidinedione (TZD) insulin sensitizers are specific agonists of peroxisome proliferator activated receptor (PPAR)gamma. However, their mechanism of action and the in vivo target tissue(s) that mediate insulin sensitization remain poorly defined. Although PPARgamma messenger RNA expression has been reported in skeletal muscle, the expression of PPARgamma within myocytes in intact muscle tissue has not been examined. An antipeptide PPARgamma antibody was generated; immunohistochemistry was then used to demonstrate that PPARgamma is present within nuclei of myocytes [in both skeletal (white and red fibers) and cardiac tissue (rodent and human)]. The effect of insulin sensitizer treatment on muscle insulin action was studied using ob/ob mice after 4 days dosing with a potent (6 nM PPARgamma Kd) TZD (10 mg/kg x day). 2-deoxyglucose (2-DOG) uptake was then assessed in freshly isolated soleus muscles from lean vs. ob/ob vs. TZD-treated ob/ob mice. In lean mouse muscles, 2-DOG uptake was stimulated by 82%, 95%, 165% (with 25, 100, 2000 microU/ml insulin); muscles from ob/ob were severely insulin resistant (<80% stimulation with 2000 microU/ml insulin). Muscles from TZD-treated ob/ob displayed a normal insulin response with 100 (71%) or 2000 (158%) microU/ml insulin. Additional studies were performed using ZDF rats treated with/without TZD for 7 days. In vivo 2-DOG glucose uptake into soleus, gastrocnemius, and diaphragm muscles was measured during euglycemic-hyperinsulinemic clamp. Compared with lean rats, muscle 2-DOG uptake in ZDF was reduced by 52% (soleus) or 71% (diaphragm). Partial (40-60%) normalization of the reduced 2-DOG uptake was evident in TZD-treated ZDF rats. In contrast to the effect of in vivo treatment on muscle insulin action, preincubation of isolated soleus muscles from naive lean or ob/ob mice for 5 h with 100 nM TZD did not affect insulin-stimulated 2-DOG uptake. We conclude: 1) PPARgamma is expressed in myocytes within skeletal and cardiac muscle. 2) In vivo activation of PPARgamma by treatment of insulin-resistant mice/rats with a potent TZD corrects impaired muscle insulin action. 3) The lack of a direct effect on muscle after 5 h in vitro TZD incubation suggests that changes in insulin action may require a longer duration of PPARgamma activation or that improved muscle insulin sensitivity may result from an indirect in vivo effect of PPARgamma activation (e.g. changes in systemic lipid metabolism).

Animals↗

The enhancer of polycomb gene of Drosophila encodes a chromatin protein conserved in yeast and mammals.

The Polycomb group of genes in Drosophila are homeotic switch gene regulators that maintain homeotic gene repression through a possible chromatin regulatory mechanism. The Enhancer of Polycomb (E(Pc)) gene of Drosophila is an unusual member of the Polycomb group. Most PcG genes have homeotic phenotypes and are required for repression of homeotic loci, but mutations in E(Pc) exhibit no homeotic transformations and have only a very weak effect on expression of Abd-B. However, mutations in E(Pc) are strong enhancers of mutations in many Polycomb group genes and are also strong suppressors of position-effect variegation, suggesting that E(Pc) may have a wider role in chromatin formation or gene regulation than other Polycomb group genes. E(Pc) was cloned by transposon tagging, and encodes a novel 2023 amino acid protein with regions enriched in glutamine, alanine and asparagine. E(Pc) is expressed ubiquitously in Drosophila embryogenesis. E(Pc) is a chromatin protein, binding to polytene chromosomes at about 100 sites, including the Antennapedia but not the Bithorax complex, 29% of which are shared with Polycomb-binding sites. Surprisingly, E(Pc) was not detected in the heterochromatic chromocenter. This result suggests that E(Pc) has a functional rather than structural role in heterochromatin formation and argues against the heterochromatin model for PcG function. Using homology cloning techniques, we identified a mouse homologue of E(Pc), termed Epc1, a yeast protein that we name EPL1, and as well as additional ESTs from Caenorhabditis elegans, mice and humans. Epc1 shares a long, highly conserved domain in its amino terminus with E(Pc) that is also conserved in yeast, C. elegans and humans. The occurrence of E(Pc) across such divergent species is unusual for both PcG proteins and for suppressors of position-effect variegation, and suggests that E(Pc) has an important role in the regulation of chromatin structure in eukaryotes.

Amino Acid Sequence↗

Enteropathy-associated T-cell lymphoma and its immunocarcinogenic correlates: case report and review of the literature.

We report a case of enteropathy-associated T-cell lymphoma (EATL), diagnosed by small intestine and gastric biopsies, who presented with manifestations of hypocalcemia and malabsorption. Immunological assessment revealed increased expression levels of tumor necrosis factor system components and eotaxin, an observation that is consistent with the cytotoxic T-cell phenotype characteristic of EATL, and decreased numbers of circulating activated (CD8+CD38+ and CD4+CD25+) and suppressor (CD11b+) T cells, a feature which can contribute to lymphomagenesis in patients with celiac disease. The acute clinical presentation of the patient resolved with mineral and vitamin supplementation and a gluten-free diet. The novel immunological findings described are discussed in the context of a review of our current knowledge of the immunopathogenesis of celiac disease and associated intestinal neoplasia.

Adult↗

Inhaled nitric oxide in infants and children after open heart surgery.

OBJECTIVE: To assess the effects of inhaled nitric oxide (NO) on oxygenation and pulmonary circulation in infants and children with critical pulmonary perfusion and/or hypoxemia after open heart surgery. STUDY: A prospective case series report. SETTING: A multidisciplinary pediatric intensive care unit in a University hospital PATIENTS: From June 1993 to March 1996 37 pediatric patients after open heart surgery were treated with inhaled NO. Their mean age was 2.9+/-0.6 years, their mean body weight 12.6+/-1.8 kg. METHODS: Inhaled NO was applied using a microprocessor controlled delivery system which continuously measured NO and NO2 by the chemilumniscence method. Monitoring included ECG, continuous pulse oximetry (SaO2), arterial (AP), central venous (CVP) and left atrial (LAP) pressures and in 8 patients a pulmonary artery (PAP) pressure. Inhaled NO was started at an SaO2 <90% with a fraction of inspired oxygen concentration (FiO2) >0.7, at a mean pulmonary artery pressure (MPAP) >50% of the mean arterial pressure (MAP), and in patients after Fontan-procedure at a CVP-LAP pressure gradient >10 mmHg. RESULTS: The mean dose of inhaled NO was 3.7+/-0.3 ppm and the mean duration was 112+/-14.7 hours. For the whole group SaO2 increased from 79.6+/-2.3 to 90.1+/-1.5% (p<0.01) within 20 minutes of NO-inhalation. Inhaled NO significantly decreased the MPAP from 47.8+/-4 to 27.5+/-2.3 mmHg (p<0.01) in 8 patients with postoperative pulmonary hypertension and significantly decreased the transpulmonary pressure (CVP-LAP) from 14.3+/-0.8 to 7.3+/-0.9 mmHg (p<0.01) in 16 patients after Glenn- or Fontan-procedure. CONCLUSIONS: Inhaled NO is very effective to decrease pulmonary artery pressure, to improve oxygenation, and to improve Fontan-circulation in infants and children after open heart surgery.

Administration, Inhalation↗

Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.

BACKGROUND: Evaluation of patients with acute chest pain in emergency rooms is time-consuming and expensive, and it often results in uncertain diagnoses. We prospectively investigated the usefulness of bedside tests for the detection of cardiac troponin T and troponin I in the evaluation of patients with acute chest pain. METHODS: In 773 consecutive patients who had had acute chest pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative bedside tests based on the use of specific monoclonal antibodies. Testing was performed on arrival and four or more hours later so that one sample was taken at least six hours after the onset of pain. The troponin T results were made available to the treating physicians. RESULTS: Troponin T tests were positive in 123 patients (16 percent), and troponin I tests were positive in 171 patients (22 percent). Among 47 patients with evolving myocardial infarction, troponin T tests were positive in 44 (94 percent) and troponin I tests were positive in all 47. Among 315 patients with unstable angina, troponin T tests were positive in 70 patients (22 percent), and troponin I tests were positive in 114 patients (36 percent). During 30 days of follow-up, there were 20 deaths and 14 nonfatal myocardial infarctions. Troponin T and troponin I proved to be strong, independent predictors of cardiac events. The event rates in patients with negative tests were only 1.1 percent for troponin T and 0.3 percent for troponin I. CONCLUSIONS: Bedside tests for cardiac-specific troponins are highly sensitive for the early detection of myocardial-cell injury in acute coronary syndromes. Negative test results are associated with low risk and allow rapid and safe discharge of patients with an episode of acute chest pain from the emergency room.

Acute Disease↗

Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.

In its severe form, X-linked adrenoleukodystrophy (ALD) is a lethal neurologic disease of children, characterized by progressive cerebral demyelination and adrenal insufficiency. Associated with a biochemical defect of peroxisomal beta-oxidation, very long-chain fatty acids (VLCFA) build up in tissues that have a high turnover of lipids, such as central nervous system (CNS) white matter, adrenal cortex, and testis. Whether the abnormal accumulation of VLCFA is the underlying cause of demyelination or merely an associated biochemical marker is unknown. ALD is caused by mutations in the gene for a peroxisomal membrane protein (ALDP) that shares structural features with ATP-binding-cassette (ABC) transporters. To analyze the cellular function of ALDP and to obtain an animal model of this debilitating disease, we have generated transgenic mice with a targeted inactivation of the ald gene. Motor functions in ALDP-deficient mice developed at schedule, and unexpectedly, adult animals appeared unaffected by neurologic symptoms up to at least 6 months of age. Biochemical analyses demonstrated impaired beta-oxidation in mutant fibroblasts and abnormal accumulation of VLCFAs in the CNS and kidney. In 6-month-old mutants, adrenal cortex cells displayed a ballooned morphology and needle-like lipid inclusions, also found in testis and ovaries. However, lipid inclusions and demyelinating lesions in the CNS were not a feature. Thus, complete absence of ALDP expression results in a VLCFA storage disease but does not impair CNS function of young adult mice by pathologic and clinical criteria. This suggests that additional genetic or environmental conditions must be fulfilled to model the early-onset and lethality of cerebral ALD in transgenic mice.

ATP Binding Cassette Transporter, Subfamily D, Mem↗