Soluble transferrin receptor and zinc protoporphyrin – competitors or efficient partners?

OBJECTIVES: Soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP) are both parameters of iron deficient erythropoiesis (IDE), the sTfR measurement is commonly regarded to be the more sensitive test. sTfR also reflects erythropoietic activity, it is increased in enhanced erythropoiesis. METHODS: We investigated the diagnostic accuracy of sTfR in assessment of iron deficiency (ID) and compared it with ZPP. The study was performed on 174 subjects, in which ID has been precisely staged. RESULTS: Individuals without ID and patients with storage iron depletion only, had normal sTfR values. Patients classified as IDE and patients with iron deficiency anemia had significantly increased sTfR. There was a good correlation between sTfR and hemoglobin (r = -0.86; P < 0.0001) and between sTfR and ZPP (r = 0.86; P < 0.0001). When diagnosing ID, ZPP was the more sensitive test. In mildly developed IDE associated with ZPP-ratios between 40 and 70 micromol/mol heme, the sTfR concentration was elevated in only 25% of the cases. Reliably elevated sTfR values were observed only in more advanced IDE, associated with ZPP > 70 mumol/mol heme. CONCLUSIONS: ZPP is not inferior to sTfR when diagnosing IDE. Given the good correlation between sTfR and ZPP and because ZPP is uninfluenced by the erythropoietic activity, sTfR and ZPP are not competitors, rather efficient partners in diagnosing anemias. By measuring ZPP and sTfR simultaneously, the diagnostic uncertainty inherent in each of them individually can be eliminated. In particular, the simultaneous determination of ZPP and sTfR enhances the diagnostic power of sTfR in assessment of the erythropoietic activity.     

Heart function and molecular biological parameters are comparable in young adult and aged rats after chronic myocardial infarction

OBJECTIVE: To test the hypothesis that IL-1beta and IL-6 play a pivotal role after myocardial infarction (MI) particularly in aged rats. METHODS: Chronic MI was induced in young adult (3.5 months) and aged (18 months) female Sprague-Dawley rats by ligation of the left coronary artery. Sham-operated animals of corresponding age served as controls. Heart function was measured by catheterization 4 weeks after MI. The expression of IL-1beta, IL-6, TGF-beta-isoforms, ANF, and components of the extracellular matrix (pro-collagen I and III, colligin, MMP-2 and TIMP2) was measured by ribonuclease protection assay. RESULTS: Aged control rats differed from young adult rats in that LV-developed pressure (LVDP) was higher (161 vs. 147 mmHg, p<0.05) in response to the elevated total peripheral resistance (0.71 vs. 0.47 mmHg ml min/kg, p<0.05). Contractility was reduced in aged controls as indicated by decreased LV dP/dt (8.106 vs. 10.606 mmHg/s, p<0.05). LV function was severely depressed in both MI groups (reduction in LVDP by about 35% and LV dP/dt by about 30%, increase in LVEDP to 24 mmHg) while RVP and RV dP/dt markedly increased by about 100%. This was not different between both MI groups. ANF expression as a marker of hypertrophy was induced in both MI groups, but less pronounced in the LV of aged rats. Also, the mRNA expression pattern was qualitatively comparable, but showed gradual differences. CONCLUSION: These results indicate that aged rats compensate well for hemodynamic overload induced by MI. Also, the mechanisms of myocardial post-MI remodeling are comparable in young adult and aged rats.     

Mice move smoothly: irrelevant object variation affects perception, but not computer mouse actions

Human–Computer Interactions pose special demands on the motor system, especially regarding the virtual tool transformations underlying typical mouse movements. We investigated whether such virtual tool-transformed movements are similarly resistant to irrelevant variation of a target object as skilled natural movements are. Results show that such irrelevant information deteriorates performance in perceptual tasks, whereas movement parameters remain unaffected, suggesting that the control of virtual tools draws on the same mechanisms as natural actions do. The results are discussed in terms of their practical utility and recent findings investigating unskilled and transformed movements in the framework of the action/perception model and the integration of tools into the body schema.     

The rehabilitation of clinical assessment for the diagnosis of pulmonary embolism

Pulmonary angiography is the gold standard for diagnosis of segmental pulmonary embolism, but no longer for subsegmental pulmonary embolism because the inter-observer agreement for angiographically documented subsegmental pulmonary embolism is only 60%. A normal rapid ELISA VIDAS D-dimer test result and a normal perfusion scan exclude pulmonary embolism with a negative predictive value of >99%, irrespective of clinical score. The positive predictive value for pulmonary embolism of a high probability VP-scan compared to pulmonary angiography is 87% indicating that 13% of patients with a high probability VP-scan do not have pulmonary embolism. The combination of a negative CUS, a low clinical score, and a non-diagnostic VP-scan safely excludes pulmonary embolism. Patients with a non-diagnostic VP-scan, a negative CUS, but a moderate to high clinical score are candidates for pulmonary angiography. The positive predictive value of helical spiral CT is >95 to 99%. The combination of a negative CUS, a low clinical score, and the presence of a clear alternative diagnosis is predicted to safely exclude pulmonary embolism. Helical spiral CT detects all clinical relevant pulmonary emboli and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic or a high-probability VP-scan. The negative predictive value during 3 months followup after a negative spiral CT for pulmonary embolism in 4 retrospective studies and 1 prospective management study was >99%. Only a small group of patients (1-2%) with a non-diagnostic spiral CT are candidates for pulmonary angiography. Therefore, it is predicted that the spiral CT will replace both VP-scanning and pulmonary angiography to safely exclude or diagnose pulmonary emboli in patients with suspected pulmonary embolism.     

Prospective pilot evaluation of a new needle prototype for endoscopic ultrasonography-guided fine-needle aspiration: comparison of cytology and histology yield

OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results.     

Epidemiology,pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management.     

Histopathological and clinical findings in renal transplants with Banff type II and III acute cellular rejection without tubulointerstitial infiltrates

According to the Banff guidelines for renal transplants, pure endothelialitis without any tubulointerstitial infiltrates (with the Banff components v?≥?1, i0, t0) has to be called acute cellular rejection (ACR). The pathophysiology of this rare lesion abbreviated as v_only is currently unclear, as well as its clinical, serological, and prognostic implications. Therefore, we conducted this retrospective comparative study. We compared all 23 biopsies with v_only from Hannover Medical School between 2003 and 2010 with 23 matched biopsies with the Banff components v?≥?1, i?≥?1, and t?≥?1 (v_plus) and 23 biopsies with v0, i0, and t0 (v0i0t0). Serological (available in 10, 11, and 14 patients, respectively), histological, and clinical data were compared. Of all biopsies, 0.4 % had findings of v_only. v_only, v_plus, and v0i0t0 only showed minimal differences in the Banff components apart from the cohort-defining components. Endothelialitis in v_only more frequently involved the arcuate arteries than the smaller preglomerular vessels compared to v_plus and vice versa. Combining histopathological data and serological data, v_only more frequently showed criteria for acute humoral rejection than v0i0t0 (albeit not persistent after the Bonferroni–Holm correction in pairwise comparisons), while there was no difference between v_only and v_plus. No difference could be demonstrated regarding clinical presentation at biopsy or outcome. Our results show minimal differences regarding clinical presentation, outcome, and histological features between v_only and v_plus. Patients with v_only should be thoroughly investigated for evidence of acute humoral rejection.     

Prognostic parameters contributing to palatal implant failures: a long-term survival analysis of 239 patients

Objective: To evaluate the demographic, radiological and therapeutic parameters that influence the overall clinical performance of palatal implants subjected to orthodontic loading. Patients and methods: The data of all patients who had received an orthodontic palatal implant for skeletal anchorage between January 1998 and December 2007 were reviewed retrospectively. The primary endpoint was the implant loss. The following parameters were assessed by univariate (log‐rank test) and multivariate (Cox's regression) analysis: (a) age and gender, (b) vertical bone height along the prospective implant axis, (c) surgeon's experience and (d) implant type. Results: Two‐hundred and thirty‐nine palatal implants were inserted in patients aged between 10 and 65 years. In all, 11/239 (4.6%) implants were lost: nine during the healing phase and two under functional loading. On univariate analysis, “surgeon's experience” was associated with a better implant survival and vice versa (P=0.0005; log‐rank test). The significance of “surgeon's experience” was confirmed by Cox's regression analysis (P=0.001; Wald test). All other parameters had no impact on implant loss. Conclusions: The survival probability of palatal implants is not related to demographic and radiological parameters. Implant losses mainly occurred early in the healing phase of the palatal implant. According to our data, “surgeon's experience” is the cornerstone of palatal implant success.