Search

Background: Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help optimize rehabilitation strategies and improve health-outcomes., Objectives: We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke., Methods: In this cross-sectional study CRF was measured as peak oxygen uptake (VO 2peak ) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS)., Results: The sample (n=74, mean age 64±13 years, 36% women) had a mean VO 2peak of 27.0±8.7 (86% of predicted). Fifty-one percent met the World Health Organization's recommendation of ≥150 min of moderate PA/week. Mean steps-per-day was 9316±4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS≥4), mean FSS score was 3.2±1.8.  Patients with impaired CRF (VO 2peak <80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta [95% CI]: 0.38 [0.15, 0.63], p=0.002) and less fatigue (unstandardized beta [95% CI]: -3.9 [-6.4, -1.6], p=0.004)., Conclusions: Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.

Our study aimed to evaluate perioperative complications following our institutional pre- and intraoperative management in cleft palate repair with Robin sequence (RS). RS patients who underwent cleft palate repair between 2000 and 2020 were retrospectively analysed. RS children with complete documentation and whose initial treatment involved the Tuebingen palatal plate (TPP) were included. Clinical records and operative charts were reviewed with regard to clinical characteristics as well as the neonatal and perioperative course. Results before and after adjustment of the anesthesiology protocol in 2014 were compared. 143 RS patients (41% male, 59% female) were included. Median pretherapeutic mixed-obstructive apnea index (MOAI) after birth was 9.4/hour (IQR 20.0). TPP treatment was associated with normalisation of the MOAI and adequate weight gain until surgery. At surgery, median age was 10 months (IQR 3), MOAI 0.1/h (IQR 0.5), and weight 8.7 kg (IQR 1.7). In 93% of cases (n = 133), the postoperative course was uneventful. Refinement of the anesthesiology protocol showed positive effects on the perioperative course and led to a reduction in perioperative events (10.7% vs. 2.9%). No severe perioperative complications occurred. We recommend the adoption of TPP treatment in the therapy of RS children. Our favourable results show that early TPP treatment minimizes perioperative complications in cleft palate repair by effectively and sustainably correcting upper airway obstruction., Competing Interests: Declaration of competing interest All authors have declared no potential conflicts of interest. There are no financial disclosures or commercial interests from any authors., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate whether guided deep breathing using a device improves breathlessness, quality of life, and breathing pattern in moderate and severe stage of chronic obstructive pulmonary disease (COPD)., Methods: In total, 150 patients participated in a double-blind randomized controlled trial in a four-week intervention and a four-month follow-up. Participants were randomized into a guided deep breathing group (GDBG), music listening group (MLG), or sitting still group (SSG). The patients' symptom score using the St George's Respiratory Questionnaire (SGRQ), and a Global Rating Change scale (GRC) was applied to measure breathlessness as primary outcome. The activity score and impact score of SRGQ, and breathing pattern were secondary outcomes., Results: Positive effects of the GDBG were detected in GRC scale in breathlessness at four weeks (p=0.03) with remaining effect compared to MLG (p=0.04), but not to SSG at four months follow-up. GDBG showed positive effect for respiratory rate (p<0.001) at four weeks follow-up. A positive significant change (p<0.05-0.01) was found in all groups of SGRQ symptom score., Conclusion: GDBG had a beneficial effect on respiratory pattern and breathlessness. MLG and SSG also yielded significant improvements., Practice Implications: Guided deep breathing may be used as a self-management procedure., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

T-cell responses towards tuberculin (purified protein derivative; PPD) or the Mycobacterium tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein-10 are indicative of prior contact with mycobacterial antigens. In this study, we investigated the exceptional case of a 75-yr-old patient who devoted more than one-third of his CD4 T-cells against PPD and ESAT-6. Antigen-specific T-cells were characterised using flow cytometric intracellular cytokine staining, ELISPOT assay, proliferation assays, and T-cell receptor spectratyping. T-cell frequencies were far above those found in age-matched controls (median 0.33%, range 0.05-6.32%) and remained at high levels for >2 yrs. The patient initially presented with haemoptysis, but active tuberculosis was ruled out by repeated analysis of sputum and bronchoalveolar lavage fluid. Skin testing was negative and haemoptyses did not have a M. tuberculosis-related aetiology. Phenotypical and functional properties of specific T-cells were consistent with a terminally differentiated effector-memory phenotype with capacity to produce interferon-γ, interleukin-2 and tumour necrosis factor-α. Epitope mapping showed that the CD4 T-cells were directed against a single peptide from ESAT-6 (amino acid 5-20) that was presented in context of HLA-DR. T-cell receptor Vβ-spectratyping and sequencing of specific CD4 T-cells revealed a prominent peak fraction of monoclonal origin. In conclusion, similar to monoclonal gammopathies of undetermined significance, this may represent the first T-cell counterpart with known specificity against M. tuberculosis.

T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.

Purpose: Breast carcinomas express the Na(+)/I() symporter and may-albeit not a routine procedure-be imaged with (123)iodide ((123)I) and (99m)technetium-pertechnetate ((99m)TcO(4)(-)) scintigraphy. The aim of our prospective study was the comparison of (99m)TcO(4)(-)--and (123)I-single-photon emission computed tomography (SPECT) with (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in patients suspicious for breast cancer., Methods: Twenty-nine (29) untreated patients suspected of having breast carcinoma were prospectively examined with thorax SPECT with (99m)TcO(4)(-) (n=19) or (123)I (n=10), respectively, and FDG-PET (n=29) prior to biopsy. Tumor-to-background ratios (TBRs) were calculated for SPECT findings. Mean and maximum standardized uptake values (SUVs) were calculated for PET findings. Findings were compared in an intra-individual lesion-to-lesion analysis., Results: In 28 of 29 patients, malignancy was verified with histopathology. In imaging the primary tumor, sensitivities of (99m)TcO(4)(-)-SPECT, (123)I-SPECT, and FDG-PET were 63%, 67%, and 89%, respectively. TBR maximum was 2.6+/-1.1 in (99m)TcO(4)()-SPECT and 2.3+/-0.6 in (123)I-SPECT. In FDG-PET, mean tumor SUV was 4.1+/-4 and maximum tumor SUV was 5.4+/-5.1. In contrast to FDG-PET, (99m)TcO(4)()-SPECT was ineffective in imaging nodal and distant metastases in the thorax, and (123)I-SPECT failed in imaging lymph node infiltrations. Distant metastases were not present in patients of the (123)I group, and the value of (123)I-SPECT was not evaluated., Conclusions: In contrast to FDG-PET, (99m)TcO(4)(-) and (123)I-SPECT are ineffective in imaging breast carcinoma in clinical practice.

The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies of different histological type. Patients with NY-ESO-1 expressing tumors have been shown to bear circulating autoantibodies against this antigen. In this study, we have assessed the NY-ESO-I autoantibody response in patients with lung cancer by a serum ELISA. Using a serum dilution of 1:400 we detected seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was significantly higher in patients suffering from non small cell lung cancer (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with undifferentiated tumors (40%) as compared to patients with either adenocarcinoma or squamous cell carcinoma (15 and 29%). Our observations indicate that induction of NY-ESO-I autoantibodies depends on the histological subtype within a given tumor entity.

The influence of dietary phytoestrogens provided by Western diets on mammographic density is not well established. Soy and soy products as source of isoflavones were found to be inversely associated with high mammographic density, a marker for breast cancer risk. Another class of phytoestrogens, the lignans, which are more frequent in Western diets, are rarely investigated. Within the European Prospective Investigation into Cancer and Nutrition cohort in Heidelberg (EPIC-Heidelberg) we explored the feasibility of mammogram collection and measurement of mammographic density in order to investigate the association between dietary phytoestrogen intake and breast density patterns. Wolfe classification was used to summarize mammographic density. Dietary habits were assessed by means of a validated food frequency questionnaire. - Out of the 505 randomly selected women, 317 (63%) returned the questionnaire and 310 (61.4%) women provided informed consent to collect mammograms. Dietary intake of seven women with dense patterns (DY) was compared with 47 women without dense patterns. A high dietary intake of fibre (p-value = 0.008) and secoisolariciresinol (p-value = 0.043) is inversely associated with non-dense breast patterns. This is also observed for a high dietary intake of soy-products (p-value = 0.004) and, in tendency, genistein (p-value = 0.069). After adjustment for energy intake and age the groups of dense and non-dense mammographic patterns were different regarding the intake of carbohydrate (p = 0.032), soy-products (p = 0.020), fibre (p = 0.046), and secoisolariciresinol (p = 0.027). - Our results suggest an inverse association between dietary lignan intake and breast density, similar to the findings for isoflavones. To our knowledge this is the first report on this association, but due to the risk of chance finding, this has to be confirmed in a study with sufficient statistical power.

A multitude of antigens has been recently identified by screening of cDNA expression libraries derived from human tumors with autologous sera. Using a phage autoantibody assay and small panels of sera derived from cancer patients or controls it has been shown that some of these antigens display cancer-associated autoantibody responses. The diagnostic and prognostic significance of these potentially cancer-related autoantibodies remains unclear until large-scale assays are developed and serological data are available for hundreds of cancer patients and controls. The major bottleneck for the development of large-scale assays are the cloning, expression and the purification of each of the respective antigens. Due to these limitations and despite the potential clinical relevance large-scale autoantibody tests are established for only a few of these tumor antigens. Here we describe an enzyme-linked immunosorbent assay, Crude lysate ELISA (CrELISA), suitable for antigens identified by expression screening based on crude lysates of antigen-expressing bacteria. This assay permits sensitive and specific autoantibody seroscreening without the need of laborious and time-consuming cloning, expression and purification of recombinant proteins. CrELISA is robust and provides a versatile high throughput procedure for the rapid evaluation of multiple antigens in large-scale serology.

Background: Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection., Methods: One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing., Results: Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6., Conclusion: Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.

Antibodies against the p53 protein are produced by some cancer patients. In some tumour entities, the presence of p53 autoantibodies have been linked to poorer survival. This study was designed to assess the prevalence and prognostic implications of p53 autoantibodies in patients with lung cancer. Serum samples of 180 patients were tested for antibodies against p53 protein using an ELISA. We studied 134 patients with primary lung cancer [histology: small cell lung carcinoma (SCLC) n=35; non-small cell lung carcinoma (NSCLC) n=99]. The control group consisted of 46 patients without lung cancer. In 17/134 (12.6%) of the cancer patients, p53 autoantibodies were detected (4/35 SCLC, 13/99 NSCLC). Most of the positive results were found in advanced stages of NSCLC (stage I-IIIA: 1/34; stage IIIB/IV: 12/65). One of the 46 control patients tested positive. Statistical analysis of survival shows no correlation with p53 antibody status in SCLC, but a significant correlation with shorter survival in NSCLC (p=0.01). After correction for stage of disease this correlation remains significant (stage IIIB/IV: p=0.02). In our series, the presence of anti-p53 autoantibodies is almost exclusively linked to the presence of malignant disease. Prognosis for patients with NSCLC, but not SCLC seems to be linked to the p53 autoantibody status.

We describe a technique for detecting an abnormal (pl 5.7) transferrin component in serum, which appears after prolonged heavy consumption of alcohol. Serum transferrin was purified by chromatography on DEAE-Affi-Gel Blue and analyzed by chromatofocusing on an ion-exchange column (Mono P). The abnormal transferrin component was detected in 17 of 20 patients (85%) with a history or prolonged consumption of alcohol (100 g per day), and in control subjects who ingested up to 80 g of alcohol per day for seven days, but not in 14 normal control subjects or 14 patients with liver disease unrelated to alcohol. The variant consistently disappeared from the serum within three weeks of cessation of alcohol consumption. It is apparently produced by desialylation of ordinary human transferrin. We find that chromatofocusing on an ion-exchange column is a sensitive and reliable technique for its identification and conclude that detection of this desialylated transferrin indicates recent prolonged alcohol ingestion.

A ferritin receptor has been detected on isolated rat hepatocytes and has been partially purified from rat liver using affinity chromatography. Isolated hepatocytes exhibit approximately 30,000 ferritin binding sites/cell with a binding association constant (Ka) of 1 x 10(8) mol-1 liter. A binding assay has been developed which utilizes a hepatic ferritin receptor coupled to a microparticulate support to facilitate separation of bound and free ligand. This method yielded a Ka of 3 x 10(8) mol-1 liter for the purified hepatic ferritin receptor. Binding of ferritin to the insolubilized receptor was partially inhibited by human lactoferrin but unaffected by 200-fold molar excess of bovine albumin, rat transferrin, or human asialoorosomucoid.

The effects of minimal acute liver injury on circulating ferritin levels have been examined in the rat both in vivo and in the isolated perfused liver. Liver damage produced by 6 mmol/kg of D-galactosamine (GalN) in vivo resulted in a marked rise in plasma ferritin levels 4 h after administration, 2 h before any significant increase in plasma aspartate transaminase. In the isolated perfused liver, damage produced by 5mM GalN introduced into the perfusate also produced an early increase in circulating ferritin before any evidence of release of intracellular enzymes, or alteration in liver histology as assessed by light microscopy was apparent. It is concluded that minimal acute liver damage results in a pronounced increase in circulating ferritin levels before other evidence of liver dysfunction. This is unlikely to be due solely to increased release from damaged cells but may rather result from an alteration in the mechanism responsible for ferritin homeostasis.

Partly desialylated transferrin was measured in the serum of subjects with chronic alcoholism, of patients with non-alcoholic-related steatohepatitis, diabetes, and other non-alcoholic liver diseases, and of healthy controls. In non-alcoholic patients and controls the maximum desialylated transferrin expressed in relation to total transferrin was 1.5%. This value was exceeded in 18 (90%) of the 20 alcoholics. By contrast, gamma-glutamyl transferase was within the reference range in 9 of the alcoholics.

1. A ferritin receptor has been isolated from porcine liver and has been partially purified using affinity chromatography. 2. A binding assay has been developed which utilizes a hepatic ferritin receptor coupled to a microparticulate support which facilitates the separation of bound and free ligand. 3. An affinity constant of 2.9 x 10(9) mol-1 litre was determined for the purified hepatic ferritin receptor. 4. The molecular weight of the receptor was estimated to be approximately 53,000 by gel electrophoresis. 5. Binding of ferritin to the insolubilized receptor was unaffected by a 100-fold excess of bovine albumin, porcine and human transferrin, and human asialo-orosomucoid. 6. Binding was specific for porcine ferritin with no demonstrable binding of rat or human ferritin.

The binding characteristics and specificity of the rat hepatic ferritin receptor were investigated using ferritins prepared from rat liver, heart, spleen, kidney and serum, human liver and serum, guinea pig liver and horse spleen as well as ferritins enriched with respect to either H- or L-type subunit composition, prepared by chromatofocusing of rat liver ferritin on Mono-P or by reverse-phase chromatography of ferritin subunits on ProRPC 5/10. No significant difference was apparent in the binding of any of the tissue ferritins, or of ferritins of predominantly acidic or basic subunit composition. However, serum ferritin bound with a lower affinity. The effect of carbohydrate on the ferritin-receptor binding was examined by glycosidase treatment of tissue and serum ferritins. Tissue ferritin binding was unaffected, while serum ferritin binding affinity was increased to that of the tissue ferritins. Inhibition of ferritin binding by lactoferrin was not due to common carbohydrate moieties as previously suggested but was due to direct binding of lactoferrin to ferritin. Therefore, carbohydrate residues do not appear to facilitate receptor-ferritin binding, and sialic acid residues present on serum ferritin may in fact interfere with binding. The results indicate that the hepatic ferritin receptor acts preferentially to remove tissue ferritins from the circulation. The lower binding affinity of serum ferritin for the ferritin receptor explains its slower in vivo clearance relative to tissue ferritins.

The relationship between serum ferritin and duodenal ferritin was examined in normal subjects and in patients with iron deficiency, secondary iron overload, or idiopathic hemochromatosis (IHC). A positive correlation between serum ferritin and duodenal ferritin concentrations was found in all groups. In the iron-overload conditions, duodenal ferritin concentration was lower at all levels of serum ferritin in comparison with normal and iron-deficient subjects. Patients with secondary iron overload did not differ from those with IHC, which indicates that any decrease in duodenal ferritin concentration was secondary to the excess body iron stores. Purified duodenal ferritin from normal subjects and patients with iron-overload conditions showed the same two distinct isoferritins by isoelectric focusing. After the oral administration of iron, two additional isoferritins were detected. These resembled the major isoferritins of liver.

The biological relevance of four iron-containing fractions previously detected in rat intestinal mucosal cells has been studied. The distribution of iron in these fractions obtained by chromatography on Sepharose 6B has been examined after in vivo and in vitro incubation of mucosal cells with 59Ce. In addition, the effects of phenobarbitone, cycloheximide, iron-deficiency and iron-loading on the uptake and distrubution of iron within the four mucosal cell fractions was studied. The iron in fraction I was mostly bound to intracellular membrane particles. Fraction II was shown to be ferritin. Fraction III contained some transferrin and also a protein of molecular weight similar to transferrin but which was not precipitable by antitransferrin antiserum. Quantited with the results of 'chaser' experiments suggested that, in addition to ferritin, at least two of the fractions (I and III) were involved in the process of iron absorption by the mucosal cell.

A radioimmunoassay (RIA) for transferrin is described. The assay uses antitransferrin antibodies covalently coupled to the particulate support Matrex Pel 102, and is simple, sensitive, reproducible, and rapid. Transferrin measurement with this assay is independent of the degree of iron saturation of the protein. The RIA was applied to the measurement of transferrin concentrations in a variety of cultured human cells. Each of 11 cell lines studied contained endogenous transferrin, but the greatest concentration was found in Chang liver cells. Red blood cells were used as a negative control.